Airway management in hospital. Russian Federation of anesthesiologists and reanimatologists guidelines (second edition, 2018)

A.A. Andreenko1, E.L. Dolbneva2, V.I. Stamov3

1 FGBVOU VO “Military Medical Academy named after S.M. Kirov” Ministry of Defence of Russia, Saint-Petersburg

2 FGBNU RNCH named by acad. B.V. Petrovsky, Moscow

3 UKB № 2 FGAOU VO “Moscow State Medical University named after I.M. Sechenov” Ministry of Health of Russia, Moscow

For correspondence: Aleksander A. Andreenko — Cand. Med. Sciences, Assistant Professor, Deputy Head of the Department of Anesthesiology and Resuscitation, FGBVOU VO “Military Medical Academy named after S.M. Kirov” Ministry of Defence of Russia, Saint-Petersburg; e-mail:

For citation: Andreenko AA, Dolbneva EL, Stamov VI. Airway management in hospital. Russian Federation of anesthesiologists and reanimatologists guidelines (second edition, 2018). Alexander Saltanov Intensive Care Herald. 2019;2:7-31.

DOI: 10.21320/1818-474X-2019-2-7-31

The review presents the clinical guidelines of the Federation of Anaesthesiology and Resuscitation specialists of Russia, revised in 2018. The recommendations are based on a review of publications and modern international guidelines of the Difficult Airway Society (DAS, 2015), American Society of Anesthesiologists (ASA, 2013), the European Society of Anesthesiologists (ESA, 2018).

“Difficult airways” are encountered relatively infrequently in modern anesthesia practice, but if it is impossible to ensure adequate oxygenation of patients, they lead to post-hypoxic brain damage or circulatory arrest. Current requirements for patient safety during anesthesia determine the need for a thorough assessment of patients before surgery, identification of prognostic signs of difficult ventilation through a face mask or supraglottic airway device, difficult laryngoscopy and tracheal intubation, difficult cricothyrotomy. As a result of the examination, the anesthesiologist is obliged to formulate the main and reserve action plan, prepare the necessary equipment, and involve specialists if necessary.

The recommendations provide evidence of the effectiveness of modern devices for ventilation and tracheal intubation. Algorithms for making decisions and actions in various situations with predictable and unpredictable “difficult airways” in patients with different risks of aspiration are proposed. An algorithm for preparing, predicting possible complications and performing extubation of the trachea is also proposed. The recommendations presented in the review are aimed at achieving the goal of increasing patient safety during general anesthesia by reducing the risk of developing critical disorders of gas exchange due to airway management problems.

Keywords: tracheal intubation, difficult airways, difficult mask ventilation, difficult laryngoscopy, difficult intubation, supraglottic airway devices, cricothyrotomy, failed intubation

Received: 25.02.2019


Practice Guidelines for Management of the Difficult Airway: An updated report by the American Society of Anesthesiologists Task Force on management of the difficult airway. Anesthesiology. 2013; 118: 251–270. DOI: 10.1097/ALN.0b013e31827773b2

Cheney F.W., Posner K.L., Lee L.A., et al. Trends in anesthesia-related death and brain damage: a closed claims analysis. Anesthesiology. 2006; 105: 1081–1086.

Domino K.B., Posner K.L., Caplan R.A., Cheney F.W. Airway injury during anesthesia: A closed claims analysis. Anesthesiology. 1999; 91: 1703–1711.

Metzner J., Posner K.L., Lam M.S., Domino K.B. Closed claims’ analysis. Best. Pract. Res. Clin. Anaesthesiol. 2011; 25(2): 263–276. DOI: 10.1016/j.bpa.2011.02.007

Miller C.G. Management of the Difficult Intubation in Closed Malpractice Claims. ASA Newsletter. 2000; 64(6): 13–16 & 19.

Cook T.M., MacDougall-Davis S.R. Complications and failure of airway management. Br. J. Anaesth. 2012 Dec;109 Suppl 1:i68-i85. DOI: 10.1093/bja/aes393.

Cook T.M., Woodall N., Frerk C.; Fourth National Audit Project. Major complications of airway management in the UK: results of the Fourth National Audit Project of the Royal College of Anaesthetists and the Difficult Airway Society. Part 1: anaesthesia. Br. J. Anaesth. 2011; 106(5): 617–631. DOI: 10.1093/bja/aer058

Долбнева Е.Л., Стамов В.И., Мизиков В.М., Бунятян А.А. «“Трудные дыхательные пути” — частота встречаемости в РФ и пути решения». Тезисы XIV Съезда Федерации анестезиологов и реаниматологов. С. 116–117. [Dolbneva E.L., Stamov V.I., Mizikov V.M., Bunyatyan A.A. «Difficult airways» is the frequency of occurrence in the Russian Federation and solutions. Tezisy XIV Sezda Federacii anesteziologov i reanimatologov. P. 116–117. (In Russ)]

Millerʼs Anesthesia, 7th Ed. By Ronald D. Miller, Lars I. Eriksson, Lee A. Fleisher, et al. Philadelphia, PA: Elsevier/Saunders, 2012.

Алгоритмы действий при критических ситуациях в анестезиологии. Рекомендации Всемирной федерации обществ анестезиологов. Под ред. Брюса Маккормика (Bruce McCormick). Русское издание под ред. Э.В. Недашковского. Архангельск: СГМА. Главы: «План интубации трахеи», «Непредвиденно сложная интубация», «Сценарий “не могу интубировать — не могу вентилировать”». [Algoritmy dejstvij pri kriticheskih situaciyah v anesteziologii. Rekomendacii vsemirnoj federacii obshchestv anesteziologov. (Algorithms for action in critical situations in anesthesiology. Recommendations of the World Federation of Anesthesiology Societies). Pod redakciej Bryusa Makkormika (Bruce McCormick). Russkoe izdanie pod red. E.V. Nedashkovskogo. Arhangelʼsk: SGMA. Glavy: “Plan intubacii trahei”, “Nepredvidenno slozhnaya intubaciya”, “Scenarij ‘ne mogu intubirovatʼ — ne mogu ventilirovatʼ”. (In Russ)]

Анестезиология: национальное руководство. Под ред. А.А. Бунятяна, В.М. Мизикова. М.: ГЭОТАР-Медиа, 2013. Серия «Национальные руководства». Мизиков В.М., Долбнева Е.Л. Глава 11. «Поддержание проходимости дыхательных путей и проблема “трудной интубации трахеи”». [Anesteziologiya: nacionalʼnoe rukovodstvo (Anesthesiology: national guidelines) Pod red. A.A. Bunyatyana, V.M. Mizikova. M.: GEOTAR-Media, 2013. (Seriya “Nacionalʼnye rukovodstva”). Mizikov V.M., Dolbneva E.L. Glava 11. “Podderzhanie prohodimosti dyhatelʼnyh putej i problema ‘trudnoj intubacii trahei’”. (In Russ)]

Буров Н.Е., Волков О.И. Тактика и техника врача-анестезиолога при трудной интубации. Клин. анестезиол. и реаниматол. 2004; 1(2): 68–74. [Burov N.E., Volkov O.I. Tactics and technique of the anesthesiologist with difficult intubation. Klinicheskaya Anesteziologiya i Reanimatologiya. 2004; 1(2): 68–74. (In Russ)]

Буров Н.Е. Протокол обеспечения проходимости дыхательных путей. (Обзор литературы и материалов совещания главн. анестезиологов МЗСР РФ. 2005). Клин. анестезиол. и реаниматол. 2005; 2(3): 2–12. [Burov N.E. Airway management (literature review). Klinicheskaya Anesteziologiya i Reanimatologiya. 2005; 2(3): 2–12. (In Russ)]

Молчанов И.В., Буров Н.Е., Пулина Н.Н., Черкавский О.Н. Алгоритм действия врача при трудной интубации. Клиническая практика. 2012; 2: 51–57. [Molchanov I.V., Burov N.E., Pulina N.N., Cherkavskij O.N. Algorithm for difficult tracheal intubation. Klinicheskaya praktika. 2012; 2: 51–57. (In Russ)]

Молчанов И.В., Заболотских И.Б., Магомедов М.А. Трудный дыхательный путь с позиции анестезиолога-реаниматолога: пособие для врачей. Петрозаводск: ИнтелТек, 2006. [Molchanov I.V., Zabolotskih I.B., Magomedov M.A. Trudnyj dyhatelʼnyj putʼ s pozicii anesteziologa-reanimatologa posobie dlya vrachej (Difficult airway from the perspective of an anesthesiologist: manual for doctors). Petrozavodsk: IntelTek, 2006. (In Russ)]

De Hert S., Staender S., Fritsch G., et al. Pre-operative evaluation of adults undergoing elective noncardiac surgery Updated guideline from the European Society of Anaesthesiology. Eur. J. Anaesthesiol. 2018; 35: 407–465. DOI: 10.1097/EJA.0000000000000817

Roth D., Pace N.L., Lee A., et al. Airway physical examination tests for detection of difficult airway management in apparently normal adult patients. Cochrane Database Syst. Rev. 2018; 5: CD008874. DOI: 10.1002/14651858.CD008874.pub2

Ferrari L.R., Bedford R.F. General anesthesia prior to treatment of anterior mediastinal masses in pediatric cancer patients.Anesthesiology. 1990; 72: 991–995.

Siyam M.A., Benhamou D. Difficult endotracheal intubation in patients with sleep apnea syndrome. Anesth. Analg. 2002; 95: 1098–1102.

Khan Z.H., Mohammadi M., Rasouli M.R., et al. The diagnostic value of the upper lip bite test combined with sternomental distance, thyromental distance, and interincisor distance for prediction of easy laryngoscopy and intubation: a prospective study. Anesth. Analg. 2009; 109: 822–824. DOI: 10.1213/ane.0b013e3181af7f0d

Tremblay M.H., Williams S., Robitaille A., Drolet P. Poor visualization during direct laryngoscopy and high upper lip bite test score are predictors of difficult intubation with the GlideScope1 videolaryngoscope. Anesth. Analg. 2008; 106: 1495–1500.

Roth D., Pace N.L., Lee A., Hovhannisyan K., et al. Airway physical examination tests for detection of difficult airway management in apparently normal adult patients. Cochrane Database of Systematic Reviews. 2018, Issue 5. Art. No.: CD008874. DOI: 10.1002/14651858.CD008874.pub2

El-Ganzouri A.R., McCarthy R.J., Tuman K.J., et al. Preoperative airway assessment: predictive value of a multivariate risk index. Anesth. Analg. 1996; 82: 1197–1204.

Wilson M.E., Spiegelhalter D., Robertson J.A., Lesser P. Predicting difficult intubation. Br. J. Anaesth. 1988; 61: 211–216.

Nørskov A.K., Rosenstock C.V., Wetterslev J., et al. Diagnostic accuracy of anaesthesiologists’ prediction of difficult airway management in daily clinical practice: a cohort study of 188 064 patients registered in the Danish Anaesthesia Database. Anaesthesia. 2015; 70: 272–281. DOI: 10.1111/anae.12955

Mallin M., Curtis K., Dawson M., Ockerse P., Ahern M. Accuracy of ultrasound-guided marking of the cricothyroid membrane before simulated failed intubation. Am. J. Emerg. Med. 2014; 32: 61–63.

Gambee A.M., Hertzka R.E., Fisher D.M. Preoxygenation techniques: Comparison of three minutes and four breaths. Anesth. Analg. 1987; 66: 468–470.

Goldberg M.E., Norris M.C., Larijani G.E., et al. Preoxygenation in the morbidly obese: A comparison of two techniques. Anesth. Analg. 1989; 68: 520–522.

Dixon B.J., Dixon J.B., Carden J.R., et al. Preoxygenation is more effective in the 25 degrees head-up position than in the supine position in severely obese patients: a randomized controlled study. Anesthesiology. 2005; 102: 1110–1115.

Altermatt F.R., Munoz H.R., Delfino A.E., Cortinez L.I. Preoxygenation in the obese patient: effects of position on tolerance to apnoea. Br. J. Anaesth. 2005; 95: 706–709. DOI: 10.1093/bja/aei231

Harbut P., Gozdzik W., Stjernfält E., et al. Continuous positive airway pressure/pressure support pre-oxygenation of morbidly obese patients. Acta Anesthesiol. Scand. 2014; 58(6): 675–680. DOI: 10.1111/aas.12317

Heinrich S., Horbach T., Stubner B., et al. Benefits of Heated and Humidified High Flow Nasal Oxygen for Preoxygenation in Morbidly Obese Patients Undergoing Bariatric Surgery: A Randomized Controlled Study. J. Obes. Bariatrics. 2014; 1(1): 7.

Patel A., Nouraei S.A.R. Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE): a physiological method of increasing apnoea time in patients with difficult airways. Anaesthesia. 2015; 70: 323–329. DOI: 10.1111/anae.12923

Badiger S., John M., Fearnley R.A., Ahmad I. Optimizing oxygenation and intubation conditions during awake fibre-optic intubation using a high-flow nasal oxygen-delivery system. Br. J. Anaesth. 2015; 115: 629–632. DOI: 10.1093/bja/aev262

Tanoubi I., Drolet P., Donati F. Optimizing preoxygenation in adults. Can. J. Anaesth. 2009; 56: 449–466. DOI: 10.1007/s12630-009-9084-z

Ramachandran S.K., Cosnowski A., Shanks A., Turner C.R. Apneic oxygenation during prolonged laryngoscopy in obese patients: a randomized, controlled trial of nasal oxygen administration. J. Clin. Anesth. 2010; 22: 164–168. DOI: 10.1016/j.jclinane.2009.05.006

Cohn A.I., Zornow M.H. Awake endotracheal intubation in patients with cervical spine disease: A comparison of the Bullard laryngoscope and the fiberoptic bronchoscope. Anesth. Analg. 1995; 81: 1283–1286.

Ovassapian A., Krejcie T.C., Yelich S.J., Dykes M.H. Awake fibreoptic intubation in the patient at high risk of aspiration. Br. J. Anaesth. 1989; 62: 13–16.

Smith C.E., Pinchak A.B., Sidhu T.S., et al. Evaluation of tracheal intubation difficulty in patients with cervical spine immobilization: Fiberoptic (WuScope) versus conventional laryngoscopy. Anesthesiology. 1999; 91: 1253–1259.

Asai T., Eguchi Y., Murao K., et al. Intubating laryngeal mask for fibreoptic intubation–particularly useful during neck stabilization. Can. J. Anaesth. 2000; 47: 843–848.

Asai T., Matsumoto H., Shingu K. Awake tracheal intubation through the intubating laryngeal mask. Can. J. Anaesth. 1999; 46: 182–184.

Frappier J., Guenoun T., et al. Airway management using the intubating laryngeal mask airway for the morbidly obese patient. Anesth. Analg. 2003; 96: 1510–1515.

Fukutome T., Amaha K., et al. Tracheal intubation through the LMA-Fastrach in patients with difficult airways. Anaesth. Intensive Care. 1998; 26: 387–391.

Nakazawa K., Tanaka N., Ishikawa S., et al. Using the intubating laryngeal mask airway (LMA-Fastrach) for blind endotracheal intubation in patients undergoing cervical spine operation. Anesth. Analg. 1999; 89: 1319–1321.

Palmer J.H., Ball D.R. Awake tracheal intubation with the intubating laryngeal mask in a patient with diffuse idiopathic skeletal hyperostosis. Anaesthesia. 2000; 55: 70–74.

Dimitriou V.K., Zogogiannis I.D., Liotiri D.G. Awake tracheal intubation using the Airtraq laryngoscope: A case series. Acta Anesthesiol. Scand. 2009; 53: 964–967. DOI: 10.1111/j.1399-6576.2009.02012.x

Suzuki A., Toyama Y., Iwasaki H., Henderson J. Airtraq for awake tracheal intubation. Anaesthesia. 2007; 62: 746–747.

Thong S.-Y., Gar-Ling Wong T. Clinical Uses of the Bonfils Retromolar Intubation Fiberscope. Anesth. Analg. 2012; 115(4): 855–866.

Takahata O., Kubota M., Mamiya K., et al. The efficacy of the ‘‘BURP’’ maneuver during a difficult laryngoscopy. Anesth. Analg. 1997; 84: 419–421.

Levitan R.M., Mechem C.C., Ochroch E.A., et al. Head-elevated laryngoscopy position: improving laryngeal exposure during laryngoscopy by increasing head elevation. Ann. Emerg. Med. 2003; 41: 322–330.

Hasegawa K., Shigemitsu K., Hagiwara Y., et al. Association between repeated intubation attempts and adverse events in emergency departments: an analysis of a multicenter prospective observational study. Ann. Emerg. Med. 2012; 60: 749–754. DOI: 10.1016/j.annemergmed.2012.04.005

Lewis S.R., Butler A.R., Parker J., et al. Videolaryngoscopy versus direct laryngoscopy for adult patients requiring tracheal intubation: a Cochrane Systematic Review. Br. J. Anaesth. 2017; 119(3): 369–383. DOI: 10.1093/bja/aex228

Marouf H.M., Khalil N. A Randomized Prospective Study Comparing C-Mac D-Blade, Airtraq, and Fiberoptic Bronchoscope for Intubating Patients with Anticipated Difficult Airway. J. Anesth. Clin. Res. 2017; 8: 766. DOI: 10.4172/2155–6148.1000766

Pieters B.M., Maas E.H., Knape J.T., van Zundert A.A. Videolaryngoscopy vs. direct laryngoscopy use by experienced anaesthetists in patients with known difficult airways: a systematic review and meta-analysis. Anaesthesia. 2017; 72(12): 1532–1541. DOI: 10.1111/anae.14057

Koh J.C., Lee J.S., Lee Y.W., Chang C.H. Comparison of the laryngeal view during intubation using Airtraq and Macintosh laryngoscopes in patients with cervical spine immobilization and mouth opening limitation. Korean J. Anesthesiol. 2010; 59: 314–318. DOI: 10.4097/kjae.2010.59.5.314

Lim Y., Yeo S.W. A comparison of the GlideScope with the Macintosh laryngoscope for tracheal intubation in patients with simulated difficult airway. Anaesth. Intensive Care. 2005; 33: 243–247.

Malik M.A., Subramaniam R., et al. Randomized controlled trial of the Pentax AWS, Glidescope, and Macintosh laryngoscopes in predicted difficult intubation. Br. J. Anaesth. 2009; 103: 761–768. DOI: 10.1093/bja/aep266

Serocki G., Bein B., Scholz J., Dörges V. Management of the predicted difficult airway: A comparison of conventional blade laryngoscopy with video-assisted blade laryngoscopy and the GlideScope. Eur. J. Anesthesiol. 2010; 27: 24–30. DOI: 10.1097/EJA.0b013e32832d328d

Aziz M.F., Dillman D., Fu R., Brambrink A.M. Comparative effectiveness of the C–MAC video laryngoscope versus direct laryngoscopy in the setting of the predicted difficult airway. Anesthesiology. 2012; 116: 629–636. DOI: 10.1097/ALN.0b013e318246ea34

Enomoto Y., Asai T., Arai T., et al. Pentax-AWS, a new videolaryngoscope, is more effective than the Macintosh laryngoscope for tracheal intubation in patients with restricted neck movements: A randomized comparative study. Br. J. Anaesth. 2008; 100: 544–548. DOI: 10.1093/bja/aen002

Jungbauer A., Schumann M., Brunkhorst V., et al. Expected difficult tracheal intubation: A prospective comparison of direct laryngoscopy and video laryngoscopy in 200 patients. Br. J. Anaesth. 2009; 102: 546–550. DOI: 10.1093/bja/aep013

Jabre P., Combes X., Leroux B., et al. Use of gum elastic bougie for prehospital difficult intubation.Am.J. Emerg. Med. 2005; 23: 552–555.

Nolan J.P., Wilson M.E. Orotracheal intubation in patients with potential cervical spine injuries. An indication for the gum elastic bougie. Anaesthesia. 1993; 48: 630–633.

Bhatnagar S., Mishra S., Jha R.R., et al. The LMA Fastrach facilitates fibreoptic intubation in oral cancer patients. Can. J. Anaesth. 2005; 52: 641–645.

Shung J., Avidan M.S., Ing R., et al. Awake intubation of the difficult airway with the intubating laryngeal mask airway. Anaesthesia. 1998; 53: 645–649.

Parnell J.D., Mills J. Awake intubation using fast-track laryngeal mask airway as an alternative to fiberoptic bronchoscopy: A case report. AANA J. 2006; 74: 429–431.

Xu M., Li X.-X., Guo X.-Y., Wang J. Shikani Optical Stylet versus Macintosh Laryngoscope for Intubation in Patients Undergoing Surgery for Cervical Spondylosis: A Randomized Controlled Trial. Chin. Med. J. Engl. 2017; 130(3): 297–302. DOI: 10.4103/0366–6999.198926

Ainsworth Q.P., Howells T.H. Transilluminated tracheal intubation. Br. J. Anaesth. 1989; 62: 494–497.

Hung O.R., Pytka S., et al. Lightwand intubation: II-Clinical trial of a new lightwand for tracheal intubation in patients with difficult airways. Can. J. Anaesth. 1995; 42: 826–830.

Kuo Y.W., Yen M.K., Cheng K.I., Tang C.S. Lightwand-guided endotracheal intubation performed by the nondominant hand is feasible.Kaohsiung J. Med. Sci. 2007; 23(10): 504–510.

Weis F.R., Hatton M.N. Intubation by use of the light wand: Experience in 253 patients. J. Oral. Maxillofac Surg. 1989; 47: 577–580; discussion 581.

Wilson W.M., Smith A.F. The emerging role of awake videolaryngoscopy in airway management. Anaesthesia. 2018; 73(9): 1058–1061. DOI: 10.1111/anae.14324

Alhomary M., Ramadan E., Curran E., Walsh S.R. Videolaryngoscopy vs. fibreoptic bronchoscopy for awake tracheal intubation: a systematic review and meta-analysis. Anaesthesia. 2018; 73(9): 1151–1161. DOI: 10.1111/anae.14299

Moore A.R., Schricker T., Court O. Awake videolaryngoscopy-assisted tracheal intubation of the morbidly obese. Anaesthesia. 2012; 67(3): 232–235. DOI: 10.1111/j.1365-2044.2011.06979.x

Mahrous R.S., Ahmed A.M. The Shikani Optical Stylet as an Alternative to Awake Fiberoptic Intubation in Patients at Risk of Secondary Cervical Spine Injury: A Randomized Controlled Trial. J. Neurosurg. Anesthesiol. 2018; 30(4): 354–358. DOI: 10.1097/ANA.0000000000000454

Vinayagam S., Dhanger S., Tilak P., Gnanasekar R. C-MAC® video laryngoscope with D-BLADE™ and Frova introducer for awake intubation in a patient with parapharyngeal mass. Saudi J. Anaesth. 2016; 10(4): 471–473.

Hegazy A.A., Kawally H., Ismail E.F., et al. Comparison between fiberoptic bronchoscope versus C–MAC video-laryngoscope for awake intubation in obese patients with predicted difficult airway. Res. Opin. Anesth. Intensive Care. 2018; 5: 134–140. DOI: 10.4103/roaic.roaic_28_17

Frerk C., Mitchell V.S., McNarry A.F., et al. Difficult Airway Society intubation guidelines working group. Difficult Airway Society 2015 guidelines for management of unanticipated difficult intubation in adults. Br. J. Anaesth. 2015; 115(6): 827–848. DOI: 10.1093/bja/aev371

Ferson D.Z., Rosenblatt W.H., Johansen M.J., et al. Use of the intubating LMA-Fastrach in 254 patients with difficult-to-manage airways. Anesthesiology. 2001; 95: 1175–1181.

Jeon H.K., So Y.K., Yang J.H., Jeong H.S. Extracorporeal oxygenation support for curative surgery in a patient with papillary thyroid carcinoma invading the trachea. J. Laryngol. Otol. 2009; 123: 807–810. DOI: 10.1017/S0022215108003216

Sendasgupta C., Sengupta G., Ghosh K., et al. Femoro-femoral cardiopulmonary bypass for the resection of an anterior mediastinal mass. Indian. J. Anaesth. 2010; 54: 565–568. DOI: 10.4103/0019–5049.72649

Neelakanta G. Cricoid pressure is effective in preventing esophageal regurgitation. Anesthesiology. 2003; 99: 242.

Difficult Airway Society Extubation Guidelines Group, Popat M., Mitchell V., Dravid R., Patel A., Swampillai C., Higgs A. Difficult Airway Society Guidelines for the management of tracheal extubation. Anaesthesia. 2012; 67(3): 318–340. DOI: 10.1111/j.1365-2044.2012.07075.x

Schnell D., Planquette B., Berger A., et al. Cuff Leak Test for the Diagnosis of Post-Extubation Stridor. J. Intensive Care Med. 2017: 885066617700095. DOI: 10.1177/0885066617700095. [Epub ahead of print] PubMed PMID: 28343416.

Keeratichananont W., Limthong T., Keeratichananont S. Cuff leak volume as a clinical predictor for identifying post-extubation stridor. J. Med. Assoc. Thai. 2012; 95(6): 752–755.

Cook T.M., MacDougall-Davis S.R. Complications and failure of airway management, BJA: British Journal of Anaesthesia. 2012; 109(suppl. 1): i68–i85. DOI: 10.1093/bja/aes393

Hubble M.W., Wilfong D.A., Brown L.H., et al. A meta-analysis of prehospital airway control techniques part II: alternative airway devices and cricothyrotomy success rates. Prehosp. Emerg. Care. 2010; 14: 515–530. DOI: 10.3109/10903127.2010.497903

Hubert V., Duwat A., Deransy R., et al. Effect of simulation training on compliance with difficult airway management algorithms, technical ability, and skills retention for emergency cricothyrotomy. Anesthesiology. 2014; 120: 999–1008. DOI: 10.1097/ALN.0000000000000138

Cook T.M., Woodall N., Frerk C. Major complications of airway management in the UK: results of the 4th National Audit Project of the Royal College of Anaesthetists and the Difficult Airway Society. Part 1 Anaesthesia, Br. J. Anaesth. 2011; 106: 617–631). DOI: 10.1093/bja/aer058

Takayesu J.K., Peak D., Stearns D. Cadaver-based training is superior to simulation training for cricothyrotomy and tube thoracostomy. Intern. Emerg. Med. 2017; 12: 99–102. DOI: 10.1007/s11739-016-1439-1

Cooper R.M., Khan S.M. Extubation and reintubation of the difficult airway. In: Hagberg C.A., editor. Benumof and Hagberg’s Airway Management. 3rd ed. Philadelphia: Elsevier-Saunders, 2012: 1018–1046.

Cooper R.M. The use of an endotracheal ventilation catheter in the management of difficult extubations. Can. J. Anaesth. 1996; 43: 90–93.

Duggan L.V., Law J.A., Murphy M.F. Brief review: Supplementing oxygen through an airway exchange catheter: efficacy, complications, and recommendations. Can. J. Anesth. 2011; 58: 560–568. DOI: 10.1007/s12630-011-9488-4

Higgs A., Swampillai C., Dravid R., et al. Re-intubation over airway exchange catheters — mind the gap (letter). Anaesthesia. 2010; 65: 859–860. DOI: 10.1111/j.1365-2044.2010.06433.x

Bergold M.N., Kahle S., Schultzik T., et al. Intubating laryngeal tube suction disposable: Initial clinical experiences with a novel device for endotracheal intubation. Anaesthesist. 2016; 65(1): 30–35. DOI: 10.1007/s00101-015-0100-0

Singh M., Kapoor D., Anand L., Sharma A. Intubating laryngeal tube suction device (iLTS-D) requires ‘Mandheeral 1 and Mandheeral 2’ manoeuvres for optimum ventilation, Southern African Journal of Anaesthesia and Analgesia. 2018; 24(2): 63–64. DOI: 10.1080/22201181.2018.1436031

Ott T., Fischer M., Limbach T., et al. The novel intubating laryngeal tube (iLTS-D) is comparable to the intubating laryngeal mask (Fastrach) — a prospective randomised manikin study. Emergency Medicine. 2015; 23: 44. DOI: 10.1186/s13049-015-0126-y

Cook T.M., Kelly F.E. Time to abandon the ‘vintage’ laryngeal mask airway and adopt second-generation supraglottic airway devices as first choice. Br. J. Anaesth. 2015; 115: 497–499. DOI: 10.1093/bja/aev156

Guo Y., Feng Y., Liang H., et al. Role of flexible fiberoptic laryngoscopy in predicting difficult intubation. Minerva Anestesiologica. 2018;84(3): 337–345. DOI: 10.23736/S0375–9393.17.12144-9

Rosenblatt W., Ianus A.I., Sukhupragarn W., et al. Preoperative endoscopic airway examination (PEAE) provides superior airway information and may reduce the use of unnecessary awake intubation. Anesth. Analg. 2011; 112: 602–607. DOI: 10.1213/ANE.0b013e3181fdfc1c

Gätke M.R., Wetterslev J. Danish Anaesthesia Database. A documented previous difficult tracheal intubation as a prognostic test for a subsequent difficult tracheal intubation in adults. Anaesthesia. 2009; 64: 1081–1088. DOI: 10.1111/j.1365-2044.2009.06057.x

Kanaya N., Kawana S., Watanabe H., et al. The utility of three-dimensional computed tomography in unanticipated difficult endotracheal intubation. Anesth. Analg. 2000; 91: 752–754.

Sepsis-induced damage to endothelial glycocalyx (literature review)

Y.Y. Ilyina, E.V. Fot, V.V. Kuzkov, M.Y. Kirov

Department of Anesthesiology, City Hospital No 1, Arkhangelsk

Department of Anesthesiology and Intensive Care, Northern State Medical University, Arkhangelsk

For correspondence: Yana Y. Ilyina, Department of Anesthesiology and Intensive Care, Northern State Medical University, Arkhangelsk; e-mail:

For citation: Ilyina YY, Fot EV, Kuzkov VV, Kirov MY. Sepsis-induced damage to endothelial glycocalyx (literature review). Alexander Saltanov Intensive Care Herald. 2019;2:2-39.

DOI: 10.21320/1818-474X-2019-2-32-39

Glycocalyx is a gel-like layer covering the surface of vascular endothelial cells. It consists of membrane-attached proteoglycans, glycosaminoglycan chains, glycoproteins, and plasma adhesive proteins. Glycocalyx plays a key role in maintaining vascular homeostasis, controls vascular permeability and the tone of the microvasculature, prevents microvascular thrombosis and regulates leukocyte adhesion. In sepsis and septic shock, damage and shedding of glycocalyx occurs. The degradation of glycocalyx is activated by reactive oxygen species and pro-inflammatory cytokines, such as tumor necrosis factor (TNF) and interleukin-1β (IL-1β). The inflammation-mediated degradation of glycocalyx leads to vascular hyperpermeability, unregulated vasodilation, microvascular thrombosis, and enhanced leukocyte adhesion. The inflammation-mediated degradation of glycocalyx leads to vascular hyperpermeability, unregulated vasodilation, microvascular thrombosis, and enhanced leukocyte adhesion. Clinical studies have demonstrated a correlation between the levels of glycocalyx components in the blood and organ dysfunction and mortality in sepsis and septic shock. Inflammation-induced damage to glycocalyx can cause a number of specific clinical effects of sepsis, including acute kidney damage, respiratory failure and liver dysfunction. Infusion therapy is an integral part of the treatment of sepsis, but super-aggressive infusion load methods (leading to hypervolemia) may increase the degradation of glycocalyx. Moreover, some markers of glycocalyx degradation, such as circulating levels of syndecan 1 or heparan sulfate, can be used as markers of endothelial dysfunction and sepsis severity.

Keywords: endothelial glycocalyx, endothelium, sepsis, septic shock, glycocalyx shedding, vascular permeability

Received: 08.02.2019


  1. Uchimido R., Schmidt E.P., Shapiro N.I. The glycocalyx: a novel diagnostic and therapeutic target in sepsis. Crit. Care. 2019; 23: 16. DOI: 10.1186/s13054-018-2292-6
  2. Colbert J.F., Schmidt E.P. Endothelial and microcirculatory function and dysfunction in sepsis. Clin. Chest. Med. 2016; 37: 263–275. DOI: 10.1016/j.ccm.2016.01.009
  3. Максименко А.В. Эндотелиальный гликокаликс — значимая составная часть двойного защитного слоя сосудистой стенки: диагностический индикатор и терапевтическая мишень. Кардиологический вестник. 2016; 11(3): 94–100. [Maksimenko A.V. endothelial glygogalyx is significant constitutive part of double protective layer into vascular wall: diagnostic index and therapeutic target. Kardiologicheskij Vestnik. 2016; 11(3): 94–100. (In Russ)]
  4. Гончар И.В., Балашов С.А.,. Валиев И.А., Мелькумянц А.М. Роль эндотелиального гликокаликса в механогенной регуляции тонуса артериальных сосудов. Труды московского физико-химического института. 2017; 1: 101–108. [Gonchar I.V., Balashov S.A., Valiev I.A., Melkumyanz А.М. The role of endothelial glycocalyx in the mechanogenic regulation of arterial vascular tone. Proceedings of the Moscow Institute of Physics and Chemistry. 2017; 1: 101–108. (In Russ)]
  5. Woodcock T.E., Woodcock T.M. Revised Starling equation and the glycocalyx model of transvascular fluid exchange: an improved paradigm for prescribing intravenous fluid therapy. Br. J. Anaesth. 2012; 108: 384–394. DOI: 10.1093/bja/aer515
  6. Frati-Munari A.C. Medical significance of endothelial glycocalyx. Arch Cardiol Mex. 2013; 83: 303–312. DOI: 10.1016/j.acmx.2013.04.015
  7. Kolářová H., Ambrůzová B., Svihálková L., et al. Modulation of endothelial glycocalyx structure under inflammatory conditions. Mediators Inflamm. 2014: ID 694312. DOI: 10.1155/2014/694312
  8. Singh A., Ramnath R.D., Foster R.R., et al. Reactive oxygen species modulate the barrier function of the human glomerular endothelial glycocalyx. PLoS One. 2013; 8(1): e55852. DOI: 10.1371/journal.pone.0055852
  9. Stehouwer C.D., Smulders YM. Microalbuminuria and risk for cardiovascular disease: analysis of potential mechanisms. J. Am. Soc. Nephrol. 2006; 17: 2106–2111. DOI: 10.1681/ASN.2005121288
  10. Forbes J.M., Coughlan M.T., Cooper ME. Oxidative stress as a major culprit in kidney disease in diabetes. Diabetes. 2008; 57: 1446–1454. DOI: 10.2337/db08–0057
  11. Adachi T., Fukushima T., Usami Y., et al. Binding of human xanthine oxidase to sulphated glycosaminoglycans on the endothelial-cell surface. Biochem J. 1993; 289: 523–527. DOI: 10.1042/bj2890523
  12. Becker M., Menger M.D., Lehr H.A. Heparin-released superoxide dismutase inhibits postischemic leukocyte adhesion to venular endothelium. Am. J. Physiol. 1994; 267: 925–930. DOI: 10.1152/ajpheart.1994.267.3.H925
  13. Becker B.F., Chappell D., Bruegger D., et al. Therapeutic strategies targeting the endothelial glycocalyx: acute deficits, but great potential. Cardiovasc. Res. 2010; 87: 300–310. DOI: 10.1093/cvr/cvq137
  14. Gouverneur M., Spaan J.A., Pannekoek H., et al. Fluid shear stress stimulates incorporation of hyaluronan into endothelial cell glycocalyx. American Journal of Physiology. Heart and Circulatory Physiology. 2006; 290: 458–462. DOI: 10.1152/ajpheart.00592.2005
  15. Johansson P.I., Henriksen H.H., Stensballe J., et al. Traumatic endotheliopathy: a prospective observational study of 424 severely injured patients. Ann. Surg. 2017; 265(3): 597–603. DOI: 10.1097/SLA.0000000000001751
  16. Gandhi N.S., Mancera R.L. The structure of glycosaminoglycans and their interactions with proteins. Chem. Biol. Drug. Des. 2008; 72(6): 455–482. DOI: 10.1111/j.1747-0285.2008.00741.x
  17. Paulus P., Jennewein C., Zacharowski K. Biomarkers of endothelial dysfunction: can they help us deciphering systemic inflammation and sepsis? Biomarkers. 2011; 16: 11–21. DOI: 10.3109/1354750X.2011.587893
  18. Reitsma S., Slaaf D.W., Vink H., et al. The endothelial glycocalyx: composition, functions, and visualization. Pflugers Archiv: European Journal of Physiology. 2007; 454: 345–359. DOI: 10.1007/s00424-007-0212-8
  19. Rehm M., Bruegger D., Christ F., et al. Shedding of the endothelial glycocalyx in patients undergoing major vascular surgery with global and regional ischemia. Circulation. 2007; 116: 1896–1906. DOI: 10.1161/circulationaha.106.684852
  20. Burke-Gaffney A., Evans T.W. Lest we forget the endothelial glycocalyx in sepsis. Crit. Care. 2012; 16: 121. DOI: 10.1186/cc11239
  21. Kozar R.A., Peng Z., Zhang R., et al. Plasma restoration of endothelial glycocalyx in a rodent model of hemorrhagic shock. Anesth. Analg. 2011; 112: 1289–1295. DOI: 10.1213/ANE.0b013e318210385c
  22. Cancel L.M., Ebong E.E., Mensah S., et al. Endothelial glycocalyx, apoptosis and inflammation in an atherosclerotic mouse model. Atherosclerosis. 2016; 252: 136–146. DOI: 10.1016/j.atherosclerosis.2016.07.930
  23. Miranda C.H., de Carvalho Borges M., Schmidt A., et al. Evaluation of the endothelial glycocalyx damage in patients with acute coronary syndrome Atherosclerosis. 2016; 247: 184–188. DOI: 10.1016/j.atherosclerosis.2016.02.023
  24. Padberg J.S., Wiesinger A., di Marco G.S. Damage of the endothelial glycocalyx in chronic kidney disease. Atherosclerosis. 2014; 234: 335–343. DOI: 10.1016/j.atherosclerosis.2014.03.016
  25. Nieuwdorp M., Mooij H.L., Kroon J., et al. Endothelial glycocalyx damage coincides with microalbuminuria in type 1 diabetes. Diabetes. 2006; 55: 1127–1132. DOI: 10.2337/diabetes.55.04.06.db05–1619
  26. Jacob M., Saller T., Chappell D., et al. Physiological levels of A-, B- and C-type natriuretic peptide shed the endothelial glycocalyx and enhance vascular permeability. Basic Res Cardiol. 2013; 108: 347. DOI: 10.1007/s00395-013-0347-z
  27. Salmon A.H., Satchell S.C. Endothelial glycocalyx dysfunction in disease: albuminuria and increased microvascular permeability. J. Pathol. 2012; 226: 562–574. DOI: 10.1002/path.3964
  28. Myburgh J.A., Mythen M.G. Resuscitation fluids. N. Engl. J. Med.. 2013; 369: 1243–1251.
  29. Henrich M., Gruss M., Weigand M.A. Sepsis-induced degradation of endothelial glycocalyx. Sci World J. 2010; 10: 917–923. DOI: 10.1100/tsw.2010.88
  30. Bruegger D., Jacob M., Rehm M. Atrial natriuretic peptide induces shedding of the endothelial glycocalyx in the coronary vascular bed of guinea pig. Am. J. Physiol. Heart Circ. Physiol. 2005; 289: 1993–1999. DOI: 10.1152/ajpheart.00218.2005
  31. Adamson R.H., Lenz J.F., Zhang X., et al. Oncotic pressures opposing filtration across non-fenestrated rat microvessels. Journal of Physiology. 2004; 557: 889–907. DOI: 10.1113/jphysiol.2003.058255
  32. Levick J.R., Michel C.C. Microvascular fluid exchange and the revised Starling principle. Cardiovascular Research. 2010; 87: 198–210. DOI: 10.1093/cvr/cvq062
  33. Ait-Oufella H., Maury E., Lehoux S., et al. The endothelium: physiological functions and role in microcirculatory failure during severe sepsis. Intensive Care Medicine. 2010; 36: 1286–1298. DOI: 10.1007/s00134-010-1893-6
  34. Pries A.R., Secomb T.W., Gaehtgens P. The endothelial surface layer. Pflugers Arch. 2000; 440: 653–666. DOI: 10.1007/s004240000307
  35. Jacob M., Bruegger D., Rehm M., et al. The endothelial glycocalyx affords compatibility of Starlingʼs principle and high cardiac interstitial albumin levels. Cardiovascular Research. 2007; 73: 575–586. DOI: 10.1016/j.cardiores.2006.11.021
  36. Florian J.A., Kosky J.R., Ainslie K., et al. Heparan sulfate proteoglycan is a mechanosensor on endothelial cells. Circ. Res. 2003; 93: 136–142. DOI: 10.1161/01.RES.0000101744.47866.D5
  37. Chelazzi C., Villa G., Mancinelli P., et al. Glycocalyx and sepsis-induced alterations in vascular permeability. Crit. Care. 2015; 19: 26. DOI: 10.1186/s13054-015-0741-z
  38. Karamysheva A.F. Mechanisms of angiogenesis. Biochemistry. 2008; 73: 751–762.
  39. Becker B.F., Jacob M., Leipert S., et al. Degradation ot the endothelial glycocalyx in clinical settings: searching for the sheddases. Br. J. Clin Pharmacol. 2015; 80: 389–402. DOI: 10.1111/bcp.12629
  40. Moseley R., Waddington R.J., Embery G. Degradation of glycosaminoglycans by reactive oxygen species derived from stimulated polymorphonuclear leukocytes. Biochim. Biophys. Acta. 1997; 1362: 221. DOI: 10.1016/S0925–4439(97)00083–5
  41. Weinbaum S., Tarbell J.M., Damiano E.R. The structure and function of the endothelial glycocalyx layer. Annu Rev. Biomed. Eng. 2007; 9: 121–167. DOI: 10.1146/annurev.bioeng.9.060906.151959
  42. Forni M., Mazzola S., Ribeiro L.A., et al. Expression of endothelin-1 system in a pig model of endotoxic shock. Regul. Pept. 2005; 131: 89–96. DOI: 10.1016/j.regpep.2005.07.001
  43. Johansson P., Stensballe J., Ostrowski S. Shock induced endotheliopathy (SHINE) in acute critical illness — a unifying pathophysiologic mechanism. Crit. Care. 2017; 21: 25. DOI: 10.1186/s13054-017-1605-5
  44. Johansson P.I., Stensballe J., Rasmussen L.S., et al. A high admission syndecan-1 level, a marker of endothelial glycocalyx degradation, is associated with inflammation, protein C depletion, fibrinolysis, and increased mortality in trauma patients. Ann. Surg. 2011; 254: 194–200. DOI: 10.1097/SLA.0b013e318226113d
  45. Steppan J., Hofer S., Funke B. Sepsis and major abdominal surgery lead to flaking of the endothelial glycocalyx. J. Surg. Res. 2011; 165: 136–141. DOI: 10.1016/j.jss.2009.04.034
  46. Ostrowski S.R., Gaïni S., Pedersen C.J., et al. Sympathoadrenal activation and endothelial damage in patients with varying degrees of acute infectious disease: An observational study. Crit. Care. 2015; 30: 90–96. DOI: 10.1016/j.jcrc.2014.10.006
  47. Haywood-Watson R.J., Holcomb J.B., Gonzalez E.A., et al. Modulation of syndecan-1 shedding after hemorrhagic shock and resuscitation. PLoS One. 2011; 6 (8): e23530. DOI: 10.1371/journal.pone.0023530
  48. Aird W.C. Endothelial cell heterogeneity. Cold Spring Harb Perspect Med. 2012; 2: a006429. DOI: 10.1101/cshperspect.a006429
  49. Ince C., Mayeux P.R., Nguyen T. The endothelium in sepsis shock. Shock. 2016; 45(3): 259–270. DOI: 10.1097/SHK.0000000000000473
  50. Zeng Y., Adamson R.H., Curry F.R.E., et al. Sphingosine-1-phosphate protects endothelial glycocalyx by inhibiting syndecan-1 shedding. Am. J. Physiol. Heart Circ. Physiol. 2014; 306: H363–H372. DOI: 10.1152/ajpheart.00687.2013
  51. Coldewey S. M, Benetti E., Collino M., et al. Elevation of serum sphingosine-1-phosphate attenuates impaired cardiac function in experimental sepsis. Sci Rep. 2016; 6: 27594. DOI: 10.1038/srep27594.
  52. Schmidt E.P, Yang Y., Janssen W.J., et al. The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis. Nat. Med. 2012; 18: 1217–1223. DOI: 10.1038/nm.2843
  53. Purushothaman A., Chen L., Yang Y., et al. Heparanase stimulation of protease expression implicates it as a master regulator of the aggressive tumor phenotype in myeloma. J. Biol. Chem. 2008; 283: 32628–32636. DOI: 10.1074/jbc.M806266200
  54. Masola V., Onisto M., Zaza G., et al. A new mechanism of action of sulodexide in diabetic nephropathy: inhibits heparanase-1 and prevents FGF-2-induced renal epithelial-mesenchymal transition. J. Transl. Med. 2012; 10: 213. DOI: 10.1186/1479-5876-10-213
  55. Song J.W., Zullo J.A., Liveris D., et al. Therapeutic restoration of endothelial glycocalyx in sepsis. J. Pharmacol. Exp. Ther. 2017; 361: 115–121. DOI: 10.1124/jpet.116.239509
  56. Yang Y., Haeger S.M., Suflita M.A., et al. Fibroblast growth factor signaling mediates pulmonary endothelial glycocalyx reconstitution. Am. J. Respir. Cell Mol. Biol. 2017; 56: 727–737. DOI: 10.1165/rcmb.2016–0338OC
  57. Rizzo A. N, Dudek S.M. Endothelial glycocalyx repair: building a wall to protect the lung during sepsis. Am. J. Respir. Cell Mol. Biol. 2017; 56: 687–688. DOI: 10.1165/rcmb.2017–0065ED
  58. Frati-Munari A.C. Medical significance of endothelial glycocalyx. Arch. Cardiol. Mex. 2013; 83: 303–312. DOI: 10.1016/j.acmx.2013.04.015
  59. Nieuwdorp M., van Haeften T.W., Gouverneur M.C., et al. Loss of endothelial glycocalyx during acute hyperglycemia coincides with endothelial dysfunction and coagulation activation in vivo. Diabetes. 2006; 55: 480–486. DOI: 10.2337/diabetes.55.02.06.db05-1103
  60. Bruegger D., Schwartz L., Chappell D., et al. Release of atrial natriuretic peptide precedes shedding of the endothelial glycocalyx equally in patients undergoing on- and off-pump coronary artery bypass surgery. Basic Res. Cardiol. 2011; 106: 1111–1121.
  61. Adamson R.H., Clark J.F., Radeva M., et al. Albumin modulates S1P delivery from red blood cells in perfused microvessels: mechanism of the protein effect. Am. J. Physiol. Heart Circ. Physiol. 2014; 306: 1011–1017. DOI: 10.1152/ajpheart.00829.2013
  62. Jacob M., Bruegger D., Rehm M., et al.Contrasting effects of colloid and crystalloid resuscitation fluids on cardiac vascular permeability. Anesthesiology. 2006; 104: 1223–1231.
  63. Jacob M., Paul O., Mehringer L., et al. Albumin augmentation improves condition of guinea pig hearts after 4 hr of cold ischemia. Transplantation. 2009; 87: 956–965. DOI: 10.1097/TP.0b013e31819c83b5
  64. Torres L.N., Sondeen J.L., Ji L., et al. Evaluation of resuscitation fluids on endothelial glycocalyx, venular blood flow, and coagulation function after hemorrhagic shock in rats. J. Trauma Acute Care Surg. 2013; 75: 759–766. DOI: 10.1097/TA.0b013e3182a92514
  65. Peng Z., Pati S., Potter D., et al. Fresh frozen plasma lessens pulmonary endothelial inflammation and hyperpermeability after hemorrhagic shock and is associated with loss of syndecan 1. Shock. 2013; 40: 195–202. DOI: 10.1097/SHK.0b013e31829f91fc
  66. Haywood-Watson R.J., Holcomb J.B., Gonzalez E.A., et al. Modulation of syndecan-1 shedding after hemorrhagic shock and resuscitation. PLoS One. 2011; 6: e23530. DOI: 10.1371/journal.pone.0023530
  67. Straat M., Müller M.C., Meijers J.C., et al. Effect of transfusion of fresh frozen plasma on parameters of endothelial condition and inflammatory status in non-bleeding critically ill patients: a prospective substudy of a randomized trial. Crit. Care. 2015; 19: 62–67. DOI: 10.1186/s13054-015-0828-6
  68. Chappell D., Hofmann-Kiefer K., Jacob M., et al. TNF-alpha induced shedding of the endothelial glycocalyx is prevented by hydrocortisone and antithrombin. Basic Res. Cardiol. 2009; 104: 78–89.
  69. De Backer D., Creteur J., Preiser J.C. Microvascular blood flow is altered in patients with sepsis. Am. J. Respir. Crit. Care Med. 2002; 166: 98–104. DOI: 10.1164/rccm.200109–016OC

Nosocomial pneumonia — principles of early diagnosis and prevention

A.N. Kuzovlev, V.V. Moroz

Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow

For correspondence: Artem N. Kuzovlev, MD, DrMed, vice-director for science, head of the laboratory of clinical pathophysiology of critical states of the V.A. Negovsky research institute of general reanimatology Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow; e-mail:

For citation: Kuzovlev AN, Moroz VV. Nosocomial pneumonia — principles of early diagnosis and prevention. Alexander Saltanov Intensive Care Herald. 2019;2:40-47.

DOI: 10.21320/1818-474X-2019-2-40-47

Nosocomial pneumonia and nosocomial tracheobronchitis present an urgent problem of anesthesiology and critical care medicine. This review presents the results of our own research on the informativity of new molecular biomarkers in the early diagnosis of nosocomial pneumonia, as well as modern principles for the prevention of nosocomial pneumonia. A promising direction for the early diagnosis of nosocomial pneumonia and its complications is the study of new molecular biomarkers, in particular, Clara cell protein and surfactant proteins. Effective prevention of nosocomial pneumonia should be based on a complex of modern evidence-based methods.

Keywords: nosocomial pneumonia, nosocomial tracheobronchitis, biomarkers, prophylaxis, sepsis, antibiotics, inhalation

Received: 23.02.2019


  1. Гельфанд Б.Р. Нозокомиальная пневмония у взрослых. Российские национальные рекомендации. М.: МИА, 2016.[Gelfand B.R. Nozokomialʼnaya pnevmoniya u vzroslyh. Rossijskie nacionalʼnye rekomendacii. M.: MIA, 2016. (In Russ)]
  2. Яковлев С.В., Суворова М.П., Белобородов В.Б., Басин Е.Е., Елисеева Е.В., Ковеленов С.В, и члены исследовательской группы ЭРГИНИ. Распространенность и клиническое значение нозокомиальных инфекций в лечебных учреждениях России: исследование ЭРГИНИ. Антибиотики и химиотерапия. 2016; 61(5–6): 32–42.[Yakovlev S.V., Suvorova M.P., Beloborodov V.B., Basin E.E., Eliseeva E.V., Kovelenov S.V, i chleny issledovatelʼskoj gruppy ERGINI. Rasprostranennostʼ i klinicheskoe znachenie nozokomialʼnyh infekcij v lechebnyh uchrezhdeniyah Rossii: issledovanie ERGINI. Antibiotiki i himioterapiya 2016; 61(5–6): 32–42. (In Russ)]
  3. Кузовлев А.Н., Шабанов А.К., Тюрин И.А. Динамика концентрации ингаляционного тобрамицина в крови и бронхоальвеолярной лаважной жидкости при нозокомиальной пневмонии (предварительное сообщение). Общая реаниматология. 2018; 14(5): 32–37. DOI: 10.15360/1813-9779-2018-5-32-37. [Kuzovlev A.N., Shabanov A.K., Tyurin I.A. Dinamika koncentracii ingalyacionnogo tobramicina v krovi i bronhoalʼveolyarnoj lavazhnoj zhidkosti pri nozokomialʼnoj pnevmonii (predvaritelʼnoe soobshchenie). Obshchaya reanimatologiya. 2018; 14(5): 32–37. DOI: 10.15360/1813-9779-2018-5-32-37. (In Russ)]
  4. Klompas M., Kleinman K., Murphy M. Descriptive epidemiology and attributive morbidity of ventilator-associated events. Infect. Control.Hosp. Epidemiol. 2014; 35(5): 502–510. DOI: 10.1086/675834
  5. Дмитриева Н.В., Петухова И.Н. Послеоперационные инфекционные осложнения. Практическое руководство. М.: Практическая медицина, 2013.[Dmitrieva N.V., Petuhova I.N. Posleoperacionnye infekcionnye oslozhneniya. Prakticheskoe rukovodstvo. Moscow: Prakticheskaya medicina, 2013. (In Russ)]
  6. Josefson P., Stralin K., Ohlin A., et al. Evaluation of a commercial multiplex PCR test (SeptiFast) in the etiological diagnosis of community-onset bloodstream infections. Eur. J. Clin. Microbiol. Infect. Dis. 2011; 30(9): 1127–1134. DOI: 10.1007/s10096-011-1201-6
  7. Мороз В.В., Голубев А.М., Кузовлев А.Н., Писарев В.М. Новые диагностические кандидатные молекулярные биомаркеры острого респираторного дистресс-синдрома. Общая реаниматология. 2014; 10(4): 6–10. DOI: 10.15360/1813-9779-2014-4-6-10. [Moroz V.V., Golubev A.M., Kuzovlev A.N., Pisarev V.M. Novye diagnosticheskie kandidatnye molekulyarnye biomarkery ostrogo respiratornogo distress-sindroma. Obshchaya reanimatologiya. 2014; 10(4): 6–10. DOI: 10.15360/1813-9779-2014-4-6-10. (In Russ)]
  8. Hayashida S, Harrod K.S., Whitsett J.A. Regulation and function of CCSP during pulmonary Pseudomonas aeruginosa infection in vivo. Am. J. Physiol. Lung. Cell. Mol. Physiol. 2000. 279(3): 452–459.
  9. Clara M. Zur Histobiologie des Bronchalepithels. [On the histobiology of the bronchial epithelium.]. Z mikrosk. Anat. Forsch. 1937; 41: 321–334.
  10. Policard A., Collet A., Giltaire-Ralyte L. Observations microélectroniques sur lʼinfrastructure des cellules bronchiolaires. [Electron microscopic observations on the ultrastructure of bronchiolar cells.] Les Bronches. 1955; 5: 187–196.
  11. Singh G., Katyal S.L. An immunologic study of the secretory products of rat Clara cells. J. Histochem. Cytochem. 1984; 32: 49–54.
  12. Snyder J., Reynolds S., Hollingsworth J., et al. Clara cells attenuate the inflammatory response through regulation of macrophage behavior. Am. J. Respir. Cell Mol. Biol. 2010; 42(2): 161–171. DOI: 10.1165/rcmb.2008–0353OC
  13. Determann R., Wolthuis E., Choi G., Bresser P., et al. Lung epithelial injury markers are not influenced by Use of Lower Tidal Volumes during Elective Surgery in Patients without Pre-existing Lung Injury. Am. J. Physiol. Lung. Cell Mol. Physiol. 2008; 294: 344–350.
  14. Negrin L.L., Halat G., Kettner S., et al. Club cell protein 16 and cytokeratin fragment 21–1 as early predictors of pulmonary complications in polytraumatized patients with severe chest trauma. PLoS One. 2017; 12(4): e0175303. DOI: 10.1371/journal.pone.0175303
  15. Lin J., Zhang W., Wang L., Tian F. Diagnostic and prognostic values of Club cell protein 16 (CC16) in critical care patients with acute respiratory distress syndrome. J. Clin. Lab. Anal. 2018; 32(2): DOI: 10.1002/jcla.22262
  16. Sorensen G.L. Surfactant Protein D in Respiratory and Non-Respiratory Diseases. Front. Med. (Lausanne). 2018; 5: 18. DOI: 10.3389/fmed.2018.00018
  17. Мороз В.В., Голубев А.М., Кузовлев А.Н. и др. Сурфактантный протеин D — биомаркер острого респираторного дистресс-синдрома. Общая реаниматология. 2013; 9(4): 11. DOI: 10.15360/1813-9779-2013-4-11. [Moroz V.V., Golubev A.M., Kuzovlev A.N., et al. Surfaktantnyj protein D — biomarker ostrogo respiratornogo distress-sindroma. Obshchaya reanimatologiya. 2013; 9(4): 11. DOI: 10.15360/1813-9779-2013-4-11. (In Russ)]
  18. King B., Kingma P. Surfactant Protein D Deficiency Increases Lung Injury during Endotoxemia. Am. J. Respir. Cell Mol. Biol. 2011; 44(5): 709–715. DOI: 10.1165/rcmb.2009–0436OC
  19. Said A., Abd-Elaziz M., Farid M., et al. Evolution of surfactant protein-D levels in children with ventilator-associated pneumonia. Pediatr Pulmonol. 2012; 47(3); 292–299. DOI: 10.1002/ppul.21548
  20. Tekerek N.U., Akyildiz B.N., Ercal B.D., Muhtaroglu S. New Biomarkers to Diagnose Ventilator Associated Pneumonia: Pentraxin 3 and Surfactant Protein D. Indian J. Pediatr. 2018; 85(6): 426–432. DOI: 10.1007/s12098-018-2607-2
  21. Park J., Pabon M., Choi A.M.K., et al. Plasma surfactant protein-D as a diagnostic biomarker for acute respiratory distress syndrome: validation in US and Korean cohorts. BMC Pulm. Med. 2017; 17(1): 204. DOI: 10.1186/s12890-017-0532-1
  22. Timsit J.F., Esaied W., Neuville M., et al. Update on ventilator-associated pneumonia. F1000Res. 2017; 6: 2061. DOI: 10.12688/f1000research.12222.1
  23. Reignier J., Darmon M., Sonneville R., et al. Impact of early nutrition and feeding route on outcomes of mechanically ventilated patients with shock: a post hoc marginal structural model study. Intensive Care Med. 2015; 41(5): 875–886. DOI: 10.1007/s00134-015-3730-4
  24. Fitch Z.W., Whitman G.J. Incidence, risk, and prevention of ventilator-associated pneumonia in adult cardiac surgical patients: a systematic review. J. Card. Surg. 2014; 29(2): 196–203. DOI: 10.1111/jocs.12260
  25. Schwebel C., Clecʼh C., Magne S., et al. Safety of intrahospital transport in ventilated critically ill patients: a multicenter cohort study. Crit. Care Med. 2013; 41(8): 1919–1928. DOI: 10.1097/CCM.0b013e31828a3bbd
  26. Bornstain C., Azoulay E., De Lassence A., et al. Sedation, sucralfate, and antibiotic use are potential means for protection against early-onset ventilator-associated pneumonia. Clin. Infect. Dis. 5; 38(10): 1401–1408.
  27. Rello J., Lode H., Cornaglia G., et al. A European care bundle for prevention of ventilator-associated pneumonia. Intensive Care Med. 2010; 36(5): 773–780. DOI: 10.1007/s00134-010-1841-5
  28. Bouadma L., Deslandes E., Lolom I., et al. Long-term impact of a multifaceted prevention program on ventilator-associated pneumonia in a medical intensive care unit. Clin Infect Dis. 2010; 51(10): 1115–1122. DOI: 10.1086/656737
  29. Muscedere J., Sinuff T., Heyland D.K., et al. The clinical impact and preventability of ventilator-associated conditions in critically ill patients who are mechanically ventilated. Chest. 2013; 144(5): 1453–1460. DOI: 10.1378/chest.13-0853
  30. Morris A.C., Hay A.W., Swann D.G., et al. Reducing ventilator-associated pneumonia in intensive care: impact of implementing a care bundle. Crit. Care Med. 2011; 39(10): 2218–2224. DOI: 10.1097/CCM.0b013e3182227d52
  31. Speck K., Rawat N., Weiner N.C., et al. A systematic approach for developing a ventilator-associated pneumonia prevention bundle. Am. J. Infect. Control. 2016; 44(6): 652–656. DOI: 10.1016/j.ajic.2015.12.020
  32. Oostdijk E.A.N., Kesecioglu .J, Schultz M.J., et al. Effects of decontamination of the oropharynx and intestinal tract on antibiotic resistance in ICUs: a randomized clinical trial. JAMA. 2014; 312(14): 1429–1437. DOI: 10.1001/jama.2014.7247
  33. Rabello F., Araújo V.E., Magalhães S. Effectiveness of oral chlorhexidine for the prevention of nosocomial pneumonia and ventilator-associated pneumonia in intensive care units: Overview of systematic reviews. Int. J. Dent. Hyg. 2018; 6(4): 441–449. DOI: 10.1111/idh.12336
  34. DeRiso A.J. II, Ladowski J.S., Dillon T.A., et al. Chlorhexidine gluconate 0.12% oral rinse reduces the incidence of total nosocomial respiratory infection and nonprophylactic systemic antibiotic use in patients undergoing heart surgery. Chest. 1996; 109(06): 1556–1561.
  35. Gjermo P. Chlorhexidine in dental practice. J. Clin. Periodontol. 1974; 1(03): 143–152.
  36. Briner W.W., Grossman E., Buckner R.Y. Effect of chlorhexidine gluconate mouthrinse on plaque bacteria. J. Periodontal. Res. 1986; 21(Suppl. 16): 44–52.
  37. Chan E.Y., Ruest A., Meade M.O., Cook D.J. Oral decontamination for prevention of pneumonia in mechanically ventilated adults: systematic review and meta-analysis. BMJ 2007; 334(7599): 889.
  38. Labeau S.O., Van de Vyver K., Brusselaers N., et al. Prevention of ventilator-associated pneumonia with oral antiseptics: a systematic review and meta-analysis. Lancet Infect. Dis. 2011; 11(11): 845–854. DOI: 10.1016/S1473–3099(11)70127-X
  39. Hua F., Xie H., Worthington H.V., et al. Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia. Cochrane Database Syst Rev 2016; 10: CD008367.
  40. Coffin S.E., Klompas M., Classen D., et al. Strategies to prevent ventilator-associated pneumonia in acute care hospitals. Infect Control. Hosp. Epidemiol. 2008; 29(Suppl. 1): 31–40.
  41. Muscedere J., Dodek P., Keenan S., Fowler R., Cook D., Heyland D.; VAP Guidelines Committee and the Canadian Critical Care Trials Group. Comprehensive evidence-based clinical practice guidelines for ventilator-associated pneumonia: diagnosis and treatment. J. Crit. Care. 2008; 23(01): 138–147. DOI: 10.1016/j.jcrc.2007.12.008
  42. Klompas M. Oropharyngeal Decontamination with Antiseptics to Prevent Ventilator-Associated Pneumonia: Rethinking the Benefits of Chlorhexidine. Semin Respir Crit. Care Med. 2017; 38(3): 381–390. DOI: 10.1055/s-0037-1602584
  43. Klompas M., Speck K., Howell M.D., et al. Reappraisal of routine oral care with chlorhexidine gluconate for patients receiving mechanical ventilation: systematic review and meta-analysis. JAMA Intern. Med. 2014; 174(05): 751–761. DOI: 10.1001/jamainternmed.2014.359
  44. Price R., MacLennan G., Glen J.; SuDDICU Collaboration. Selective digestive or oropharyngeal decontamination and topical oropharyngeal chlorhexidine for prevention of death in general intensive care: systematic review and network meta-analysis. BMJ 2014; 348: g2197. DOI: 10.1136/bmj.g2197
  45. Klompas M., Li L., Kleinman K., et al. Associations between ventilator bundle components and outcomes. JAMA Intern. Med. 2016; 176(09): 1277–1283. DOI: 10.1001/jamainternmed.2016.2427
  46. Hirata K., Kurokawa A. Chlorhexidine gluconate ingestion resulting in fatal respiratory distress syndrome. Vet. Hum. Toxicol. 2002; 44(02): 89–91.
  47. Kempen P.M. A tale of silent aspiration: are guidelines good for every patient? Anesth. Analg. 2015; 121(03): 829–831. DOI: 10.1213/ANE.0000000000000852
  48. Orito K., Hashida M., Hirata K., et al. Effects of single intratracheal exposure to chlorhexidine gluconate on the rat lung. Drug. Chem. Toxicol. 2006; 29(01): 1–9.
  49. Xue Y., Zhang S., Yang Y., et al. Acute pulmonary toxic effects of chlorhexidine (CHX) following an intratracheal instillation in rats. Hum. Exp. Oxicol. 2011; 30(11): 1795–1803. DOI: 10.1177/0960327111400104
  50. Massano G., Ciocatto E., Rosabianca C., et al. Striking aminotransferase rise after chlorhexidine self-poisoning. Lancet. 1982; 1(8266): 289.
  51. Plantinga N.L., Wittekamp B.H., Leleu K., et al. Oral mucosal adverse events with chlorhexidine 2 % mouthwash in ICU. Intensive Care Med. 2016; 42(04): 620–621. DOI: 10.1007/s00134-016-4217-7
  52. Deschepper M., Waegeman W., Eeckloo K., et al. Effects of chlorhexidine gluconate oral care on hospital mortality: a hospital-wide, observational cohort study. Intensive Care Med. 2018; 44(7): 1017–1026. DOI: 10.1007/s00134-018-5171-3
  53. Klompas M. What is new in the prevention of nosocomial pneumonia in the ICU? Curr. Opin. Crit. Care. 2017; 5: 378–384. DOI: 10.1097/MCC.0000000000000443
  54. Wang L., Li X., Yang Z., et al. Semi-recumbent position versus supine position for the prevention of ventilator-associated pneumonia in adults requiring mechanical ventilation. Cochrane Database Syst. Rev. 2016; 1: CD009946. DOI: 10.1002/14651858.CD009946.pub2
  55. Li Bassi G., Panigada M., Ranzani O.T., et al. Multicenter randomized clinical trial of lateral-trendelenburg vs. semi recumbent position for the prevention of ventilator-associated pneumonia — the GRAVITY-VAP Trial. Intensive Care Med. 2017; 43(11): 1572–1584. DOI: 10.1007/s00134-017-4858-1
  56. Esteban A., Frutos F., Tobin M.J., et al. A comparison of four methods of weaning patients from mechanical ventilation. Spanish Lung Failure collaborative Group. N. Engl. J. Med. 1995; 332: 345–350.
  57. Ely E.W., Baker A.M., Dunagan D.P., et al. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N. Engl. J. Med. 1996; 335: 1864–1869.
  58. Kress J.P., Pohlman A.S., O’Connor M.F., Hall J.B. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N. Engl. J. Med. 2000; 342: 1471–1477.
  59. Girard T.D., Kress J.P., Fuchs B.D., et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (awakening and breathing controlled trial): a randomised controlled trial. Lancet. 2008; 371: 126–134.
  60. Caroff D.A., Li L., Muscedere J., Klompas M. Subglottic secretion drainage and objective outcomes: a systematic review and meta-analysis. Crit. Care Med. 2016; 44: 830–840. DOI: 10.1097/CCM.0000000000001414
  61. Bo L., Li J., Tao T., et al. Probiotics for preventing ventilator-associated pneumonia. Cochrane Database Syst. Rev. 2014; 10: CD009066. DOI: 10.1002/14651858.CD009066.pub2
  62. Zeng J., Wang C.T., Zhang F.S., et al. Effect of probiotics on the incidence of ventilator-associated pneumonia in critically ill patients: a randomized controlled multicenter trial. Intens Care Med. 2016; 42: 1018–1028. DOI: 10.1007/s00134-016-4303-x
  63. Cook D.J., Johnstone J., Marshall J.C., et al. Probiotics: prevention of severe pneumonia and endotracheal colonization trial-PROSPECT: a pilot trial. Trials. 2016; 17: 377. DOI: 10.1186/s13063-016-1495-x
  64. Weng H., Li J.G., Mao Z., Feng Y., et al. Probiotics for Preventing Ventilator-Associated Pneumonia in Mechanically Ventilated Patients: A Meta-Analysis with Trial Sequential Analysis. Front Pharmacol. 2017; 8: 717. DOI: 10.3389/fphar.2017.00717
  65. Bos L.D., Stips C., Schouten L.R., et al. Selective decontamination of the digestive tract halves the prevalence of ventilator-associated pneumonia compared to selective oral decontamination. Intensive Care Med. 2017; 43(10): 1535–1537. DOI: 10.1007/s00134-017-4838-5
  66. Daneman N., Sarwar S., Fowler R.A., et al. Effect of selective decontamination on antimicrobial resistance in intensive care units: a systematic review and meta-analysis. Lancet Infect. Dis. 2013; 13: 328–341. DOI: 10.1016/S1473–3099(12)70322–5
  67. Russell C.J., Shiroishi M.S., Siantz E., et al. The use of inhaled antibiotic therapy in the treatment of ventilator-associated pneumonia and tracheobronchitis: a systematic review. BMC Pulm. Med. 2016; 8; 16: 40. DOI: 10.1186/s12890-016-0202-8
  68. Póvoa F.C.C., Cardinal-Fernandez P., Maia I.S., et al. Effect of antibiotics administered via the respiratory tract in the prevention of ventilator-associated pneumonia: A systematic review and meta-analysis. J. Crit. Care. 2018; 43: 240–245. DOI: 10.1016/j.jcrc.2017.09.019

Failures of intensive treatment of multiple organ failure: pathophysiology and the need for personalization

E.V. Grigoryev1,2, D.L. Shukevich1,2, G.P. Plotnikov3, A.N. Kudryavtsev3, A.S. Radivilko1

Scientific Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo

Kemerovo State Medical University, Kemerovo

A.V. Vishnevsky National Medical Research Centre of Surgery, Moscow

For correspondence: Evgeny V Grigoryev, M.D., Ph.D., Head of Chair of Anesthesiology and Reanomation, Kemerovo State Medical University, Kemerovo; e-mail:

For citation: Grigoryev EV, Shukevich DL, Plotnikov GP, Kudryavtsev AN, Radivilko AS. Failures of intensive treatment of multiple organ failure: pathophysiology and the need for personalization. Alexander Saltanov Intensive Care Herald. 2019;2:48-57.

DOI: 10.21320/1818-474X-2019-2-48-57

Multiple organ failure (MOF) is the most severe outcome of the critical care patients of any reason (sepsis, trauma, ischemia and reperfusion), the mortality rate with this syndrome has no tendency to decrease. The review article offers, first of all, an introduction to the key research areas in which the MOF theory is currently developing (alarmines, mitochondrial dysfunction, barrier insufficiency, immunological and neurological conjugation, forms of programmed cell death, induced immunosuppression, resolution of inflammation). Studies prove the feasibility of introducing a personalized approach to the diagnosis of MOF by substantiating the endophenotype of the critical care patients on the basis of a complex of immunological, genomic and clinical indicators.

Keywords: systemic inflammatory response, multiple organ failure, alarmines, mitochondria, immune suppression, barrier deficiency, endophenotype

Received: 22.02.2019


  1. Ciesla D.J., Moore E.E., Johnson J.L., et al. A 12-year prospective study of postinjury multiple organ failure: has anything changed? Arch. Surg. 2005; 140(5): 432–438. DOI: 10.1001/archsurg.140.5.432
  2. Davidson G.H., Hamlat C.A., Rivara F.P., et al. Long-term survival of adult trauma patients. JAMA. 2011; 305(10): 1001–1007. DOI: 10.1001/jama.2011.259
  3. Eiseman B., Beart R., Norton L. Multiple organ failure. Surg. Gynecol. Obstet. 1977; 144(3): 323–326.
  4. Deitch E.A., Vincent J.L., Windsor A. Sepsis and multiple organ dysfunction: multidisciplinary approach. Philadelphia: WB Sanders company, 2002.
  5. Minei J.P., Cuschieri J., Sperry J., et al. The changing pattern and implications of multiple organ failure after blunt injury with hemorrhagic shock. Crit. Care Med. 2012; 40(4): 1129–1135. DOI: 10.1097/CCM.0b013e3182376e9f
  6. Lelubre C., Vincent J.L. Mechanisms and treatment of organ failure in sepsis. Nature Review. Nephrology. 2018; 14: 417–427. DOI: 10.1038/s41581-018-0005-7
  7. Григорьев Е.В., Плотников Г.П., Шукевич Д.Л., Головкин А.С. Персистирующая полиорганная недостаточность. Патология кровообращения и кардиохирургия. 2014; 18(3): 82–86.DOI: 10.21688/1681-3472-2014-3-82-86. [Grigoryev Ye.V., Plotnikov G.P., Shukevich D.L., Golovkin A.S. Persistent multiorgan failure. Patologiya krovoobrascheniya i kardiohirurgiya. Circulation Pathology and Cardiac Surgery. 2014; 18(3): 82–86. (In Russ)]
  8. Schaefer L. Complexity of danger: The diverse nature of damage-associated molecular patterns. J. Biol.  Chem. 2014; 289: 35237–35245. DOI: 10.1074/jbc.R114.619304
  9. Ma K.C., Schenck E.J., Pabon M.A., Choi A.M.K. The role of danger signals in the pathogenesis and perpetuation of critical illness. Am. J. Respir. Crit. Care Med. 2018; 197(3): 300–309. DOI: 10.1164/rccm.201612–2460PP
  10. Zhang Q., Raoof M., Chen Y., et al. Circulating mitochondrial DAMPs cause in inflammatory responses to injury. Nature. 2010; 464: 104–107. DOI: 10.1038/nature08780
  11. Harris H.E., Raucci A. Alarmin(g) news about danger: Workshop on innate danger signals and HMGB1. EMBO Rep. 2006; 7: 774–778. DOI: 10.1038/sj.embor.7400759
  12. Guo H., Callaway J.B., Ting J.P. Infammasomes: Mechanism of action, role in disease, and therapeutics. Nat. Med. 2015; 21: 677–687. DOI: 10.1038/nm.3893
  13. Cobb J.P., Buchman T.G., Karl I.E., Hotchkiss R.S. Molecular biology of multiple organ dysfunction syndrome: Injury, adaptation, and apoptosis. Surg. Infect (Larchmt). 2000; 1: 207–213; discussion 214. DOI: 10.1089/109629600750018132
  14. Conrad M., Angeli J.P., Vandenabeele P., Stockwell B.R. Regulated necrosis: Disease relevance and therapeutic opportunities. Nat. Rev. Drug. Discov. 2016; 15: 348–366. DOI: 10.1038/nrd.2015.6
  15. Kaczmarek A., Vandenabeele P., Krysko D.V. Necroptosis: The release of damage-associated molecular patterns and its physiological relevance. Immunity. 2013; 38: 209–223. DOI: 10.1016/j.immuni.2013.02.003
  16. Krysko D.V., Agostinis P., Krysko O., et al. Emerging role of damage-associated molecular patterns derived from mitochondria in inflammation. Trends Immunol. 2011; 32: 157–164. DOI: 10.1016/
  17. Zhang Q., Raoof M., Chen Y., et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010; 464: 104–107. DOI: 10.1038/nature08780
  18. Deutchman C.S., Tracey K.J. Sepsis: Current dogma and new perspectives. Immunity. 2014; 40: 463–475. DOI: 10.1016/j.immuni.2014.04.001
  19. Bosmann M., Ward P.A. The inflammatory response in sepsis. Trends Immunol. 2013; 34: 129–136. DOI: 10.1016/
  20. Matsuda N. Alert cell strategy in SIRS-induced vasculitis: sepsis and endothelial cells Journal of Intensive Care. 2016; 4: 21. DOI: 10.1186/s40560-016-0147-2
  21. Johansson P.I., Henriksen H.H., Stensballe J., et al. Traumatic endotheliopathy: a prospective observational study of 424 severely injured patients. Ann. Surg. 2017; 265(3): 597–603. DOI: 10.1097/SLA.0000000000001751
  22. Hirase T, Node K. Endothelial dysfunction as a cellular mechanism for vascular failure. Am. J. Physiol. Heart Circ. Physiol. 2012; 302(3): 499–505. DOI: 10.1152/ajpheart.00325.2011
  23. Aird W.C. The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood. 2003; 101(10): 3765–3777. DOI: 10.1182/blood-2002-06-1887
  24. Szotowski B., Antoniak S., Rauch U. Alternatively spliced tissue factor: a previously unknown piece in the puzzle of hemostasis. Trends Cardiovasc. Med. 2006; 16(5): 177–182. DOI: 10.1016/j.tcm.2006.03.005
  25. Monroe D.M., Key N.S. The tissue factor-factor VIIa complex: procoagulant activity, regulation, and multitasking. J. Thromb. Haemost. 2007; 5(6): 1097–1105. DOI: 10.1111/j.1538-7836.2007.02435.x
  26. Danese S., Vetrano S., Zhang L., et al. The protein C pathway in tissue inflammation and injury: pathogenic role and therapeutic implications. Blood. 2010; 115(6): 1121–1130. DOI: 10.1182/blood-2009-09-201616
  27. Brinkmann V., Zychlinsky A. Beneficial suicide: why neutrophils die to, make NETs. Nature Rev. 2007; 5: 577–582. DOI: 10.1038/nrmicro1710
  28. Camicia G., Pozner R., de Larrañaga G. Neutrophil extracellular traps in Sepsis. Shock. 2014; 42(4): 286–294. DOI: 10.1097/SHK.0000000000000221
  29. Wang X., Qin W., Sun B. New strategy for sepsis: Targeting a key role of platelet-neutrophil interaction. Burns Trauma. 2014; 2(3): 114–120. DOI: 10.4103/2321–3868.135487
  30. Salmon A.H., Satchell S.C. Endothelial glycocalyx dysfunction in disease: albuminuria and increased microvascular permeability. J. Pathol. 2012; 226: 562–574. DOI: 10.1002/path.3964
  31. Pries A.R., Secomb T.W., Gaehtgens P. The endothelial surface layer. Pflugers Arch. 2000; 440: 653–666. DOI: 10.1007/s004240000307
  32. Reitsma S., Slaaf D.W., Vink H., et al. The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch. 2007; 454: 345–359. DOI: 10.1007/s00424-007-0212-8
  33. Lekakis J., Abraham P., Balbarini A., et al. Methods for evaluating endothelial function: a position statement from the European Society of Cardiology Working Group on Peripheral Circulation. Eur. J. Cardiovasc. Prev. Rehabil. 2011; 18: 775–789. DOI: 10.1177/1741826711398179
  34. Woodcock T.E., Woodcock T.M. Revised Starling equation and the glycocalyx model of transvascular fluid exchange: an improved paradigm for prescribing intravenous fluid therapy. Br. J. Anaesth. 2012; 108: 384–394. DOI: 10.1093/bja/aer515
  35. Chelazzi C., Villa G., Mancinelli P. Glycocalyx and sepsis-induced alterations in vascular permeability. Crit. Care. 2015; 19(1): 26. DOI: 10.1186/s13054-015-0741-z
  36. Uchimido R., Schmidt E.P., Shapiro N.I. The glycocalyx: a novel diagnostic and therapeutic target in sepsis. Crit. Care. 2019; 23(1): 16. DOI: 10.1186/s13054-018-2292-6
  37. Steppan J., Hofer S., Funke B., et al. Sepsis and major abdominal surgery lead to flaking of the endothelial glycocalyx. J. Surg. Res. 2011; 165: 136–141. DOI: 10.1016/j.jss.2009.04.034
  38. Tracey K.J. The inflammatory reflex. Nature. 2002; 420: 853–859. DOI: 10.1038/nature01321
  39. Tracey K.J. Physiology and immunology of the cholinergic antiinflammatory pathway. J. Clin. Invest. 2007; 117: 289–296. DOI: 10.1172/JCI30555
  40. Григорьев Е.В., Шукевич Д.Л., Плотников Г.П. и др. Нейровоспаление в критических состояниях: механизмы и протективная роль гипотермии. Фундаментальная и клиническая медицина. 2016; 1(3): 88–96. [Grigoryev E.V., Shukevich D.L., Plotnikov G.P., et al. Neuroinflammation in critical care: neuroprotective role role of hypothermia. Fundamental and clinical medicine. 2016; 1(3): 88–96. (In Russ)]
  41. Qin S., Wang H., Yuan R., et al. Role of HMGB1 in apoptosis mediated sepsis lethality. J. Exp. Med. 2006; 203: 1637–1642. DOI: 10.1084/jem.20052203
  42. Lu H., Wen D., Wang X., et al. Host genetic variants in sepsis risk: a field synopsis and meta-analysis. Crit. Care. 2019; 23(1): 26. DOI: 10.1186/s13054-019-2313-0
  43. Thayer J.F., Sternberg E.M. Neural aspects of immunomodulation: focus on the vagus nerve. Brain Behav. Immun. 2010; 24: 1223–1228. DOI: 10.1016/j.bbi.2010.07.247
  44. Karbowski M., Youle R.J. Dynamics of mitochondrial morphology in healthy cells and during apoptosis. Cell Death. Differ. 2003, 10: 870–880. DOI: 10.1038/sj.cdd.4401260
  45. Kuznetsov A.V., Kehrer I., Kozlov A.V., et al. Mitochondrial ROS production under cellular stress: comparison of different detection methods. Anal. Bioanal. Chem. 2011, 400: 2383–2390. DOI: 10.1007/s00216-011-4764-2
  46. Li C., Jackson R.M. Reactive species mechanisms of cellular hypoxia-reoxygenation injury. Am. J. Physiol. Cell Physiol. 2002; 282: 227–241. DOI: 10.1152/ajpcell.00112.2001
  47. Pellegrini M., Baldari C.T. Apoptosis and oxidative stress-related diseases: the p66Shc connection. Curr. Mol. Med. 2009; 9: 392–398. DOI: 10.2174/156652409787847254
  48. Butow R.A., Avadhani N.G. Mitochondrial signalling: the retrograde response. Mol. Cell. 2004, 14: 1–15. DOI: 10.1016/S1097–2765(04)00179–0
  49. Wendel M., Heller A.R. Mitochondrial function and dysfunction in sepsis. Wien. Med. Wochenschr. 2010; 160: 118–123. DOI: 10.1007/s10354-010-0766-5
  50. Basanez G., Zhang J., Chau B.N., et al. Pro-apoptotic cleavage products of Bcl-xL form cytochrome c-conducting pores in pure lipid membranes. J. Biol. Chem. 2001, 276: 31083–31091. DOI: 10.1074/jbc.M103879200
  51. Orrenius S., Gogvadze A., Zhivotovsky B. Mitochondrial oxidative stress: implications for cell death. Annu Rev. Pharmacol. Toxicol. 2007, 47: 143–183. DOI: 10.1146/annurev.pharmtox.47.120505.105122
  52. Glick D., Barth S., Macleod K.F. Autophagy: cellular and molecular mechanisms. J. Pathology. 2010; 221: 3–12. DOI: 10.1002/path.2697
  53. Lee I., Huttemann M. Energy crisis: the role of oxidative phosphorylation in acute inflammation and sepsis. Biochim. Biophys. Acta. 2014; 1842(9): 1579–1586. DOI: 10.1016/j.bbadis.2014.05.031
  54. Merz T.M., Pereira A.J., Schürch R., et al. Mitochondrial function of immune cells in septic shock: A prospective observational cohort study. PLoS One. 2017; 12(6): e0178946. DOI: 10.1371/journal.pone.0178946
  55. Grigoryev E.V., Shukevich D.L., Matveeva V.G., Kornekyuk R.A. Immunosuppression as a component of multiple organ dysfunction syndrome following cardiac surgery. Complex issues of cardiovascular diseases. 2018; 7(4): 84–91. DOI: 10.17802/2306-1278-2018-7-4-84-91
  56. Boomer J.S., Green J.M., Hotchkiss R.S. The changing immune system in sepsis: Is individualized immuno-modulatory therapy the answer? Virulence. 2014; 5(1), 45–56. DOI: 10.4161/viru.26516
  57. Rock K.L., Latz E., Ontiveros F., Kono H. The sterile inflammatory response. Annu Rev. Immunol. 2010; 28: 321–342. DOI: 10.1146/annurev-immunol-030409-101311
  58. Warren O.J., Smith A.J., Alexiou C., et al. The inflammatory response to cardiopulmonary bypass: part 1 — mechanisms of pathogenesis. Journal of cardiothoracic and vascular anaesthesia. 2009; 23(2): 223–231. DOI: 10.1053/j.jvca.2008.08.007
  59. Callahan L.A., Supinski G.S. Sepsis-induced myopathy. Crit. Care Med. 2009; 37(10 Suppl.): 354–367. DOI: 10.1007/s13539-010-0010-6
  60. Hermans G., Van den Berghe G. Clinical review: intensive care unit acquired weakness. Crit. Care. 2015; 19(1): 274. DOI: 10.1186/s13054-015-0993-7
  61. Klaude M., Mori M., Tjader I., et al. Protein metabolism and gene expression in skeletal muscle of critically ill patients with sepsis. Clin. Sci (Lond.). 2012; 122(3): 133–142. DOI: 10.1042/CS20110233
  62. Preiser J.-C. High protein intake during the early phase of critical illness: yes or no? Crit. Care. 2018; 22: 261. DOI: 10.1186/s13054-018-2196-5
  63. Cuenca A.G., Cuenca A.L., Winfield R.D., et al. Novel role for tumor-induced expansion of myeloid-derived cells in cancer cachexia. J. Immunol. 2014; 192(12): 6111–6119. DOI: 10.4049/jimmunol.1302895
  64. Mittal R., Coopersmith C.M. Redefining the gut as the motor of critical illness. Trends Mol. Med. 2014; 20: 214–223. DOI: 10.1016/j.molmed.2013.08.004
  65. Moore F.A., Moore E.E., Poggetti R. Gut bacterial translocation via the portal vein: A clinical perspective with major torso trauma. J. Trauma. 1991; 31: 629–636.
  66. Assimakopoulos S.F., Triantos C., Thomopoulos K., et al. Gut-origin sepsis in the critically ill patient: pathophysiology and treatment. Infection. 2018; 46(6): 751–760. DOI: 10.1007/s15010-018-1178-5
  67. Zahs A., Bird M.D., Ramirez L., et al. Inhibition of long myosin light chain kinase activation alleviates intestinal damage after binge ethanol exposure and burn injury. Am. J. Physiol. Gastrointest Liver Physiol. 2012; 303: G705–G712. DOI: 10.1152/ajpgi.00157.2012
  68. Nathan C., Ding A. Nonresolving inflammation. Cell. 2010; 140 (6): 871–882. DOI: 10.1016/j.cell.2010.02.029
  69. Carcillo J.A., Halstead E.S., Hall M.W., et al. Three Hypothetical Inflammation Pathobiology Phenotypes and Pediatric Sepsis-Induced Multiple Organ Failure Outcome. Pediatric Critical Care Medicine. 2017, 18(6): 513–523. DOI: 10.1097/PCC.0000000000001122
  70. Scicluna B.P., Vught L.A., Zwinderman A.H, et al., on behalf of the MARS consortium. Classification of patients with sepsis according to blood genomic endotype: a prospective cohort study. Lancet Respir. Med. 2017. DOI: 10.1016/S2213–2600(17)30294-1

Perioperative management of patients with adrenal insufficiency

P.V. Dunts1,2, O.E. Li2, V.B. Shumatov1

1 Pacific State Medical University, Vladivostok

2 Regional Clinical Hospital, Vladivostok

For correspondence: Pavel V. Dunts, PhD, Chief of the Department of Anesthesiology and Reanimatology of the Regional Clinical Hospital № 2, Assistant Professor of the Department of Anesthesiology and Reanimatology, Pacific State Medical University; e-mail:

For citation: Dunts PV, Li OE, Shumatov VB. Perioperative management of patients with adrenal insufficiency. Alexander Saltanov Intensive Care Herald. 2019;1:58–65.

DOI: 10.21320/1818-474X-2019-1-58-65

The article is a review of modern publications covering the issues of adrenal insufficiency in patients in the periopreparative period. The article covers the issues of epidemiology, etiology and pathogenesis, presents algorithms for examining patients with adrenal insufficiency. Topical issues such as the perioperative management of patients receiving steroid hormone replacement therapy, depending on the incidence of the operation and the problems of the hypoadrenal crisis are considered.

Keywords: adrenal insufficiency, perioperative management, anesthesia, hypoadrenal crisis

Received: 24.12.2019


  1. Фадеев В.В. Мельниченко Г.А. Надпочечниковая недостаточность. РМЖ. 2001; 24: 1088–1095. [Fadeyev V.V., Melnichenko G.А. Adrenal insufficiency. RMJ. 2001; 24: 1088–1095. (In Russ)]
  2. Федеральные клинические рекомендации (протоколы) по ведению детей с эндокринными заболеваниями. Под ред. И.И. Дедова, В.А. Петерковой. М.: Практика, 2014. [Federal clinical guidelines (protocols) for the management of children with endocrine diseases. Ed. by Dedov I., Peterkova V. M.: Practice, 2014. (In Russ)]
  3. Эндокринология. Национальное руководство. Краткое издание. Под ред. И.И. Дедова, Г.А. Мельниченко. М.: ГЕОТАР-Медиа, 2011. [Endocrinology. National leadership. Brief Editio. Ed. by Dedov I., Melnichenko G. M: GEOTAR-Media, 2011. (In Russ)]
  4. Henderson K. The Washington Manual Endocrinology. Lippincott: Willisms & Wilkins, 2004.
  5. Bornstein S.R., Allolio B., Arlt W., et al. Diagnosis and treatment of primary adrenal insufficiency: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 2016; 101(2): 364–389. DOI: 10.1210/jc.2015-1710
  6. Greenspan T.S., Gardener D. Basic and clinical endocrinology. McGraw-Hill, 2004.
  7. Boumpas D.T., Chrousos G.P., Wilder R., et al. Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. Ann. Intern. Med. 1993; 119(12): 1198–1208.
  8. Savage M.W., Mah P.M., Weetman A.P., Newell-Price J. Endocrine emergencies. Postgrad. Med. J. 2004; 80(947): 506–515.
  9. Besser G.M., Thorner M.O. Comprehensive clinical endocrinology. Edinburgh: Elsevier Science, 2002.
  10. Интенсивная терапия. Национальное руководство. Краткое издание. Под ред. Б.Р. Гельфанда, И.Б. Заболотских. 2-е изд., перераб. и доп. М.: ГЭОТАР-Медиа, 2019. [Intensive therapy. National leadership. Brief Edition. Ed. by Gelfand B., Zabolotskyh I. 2nd ed., revised and add. M.: GEOTAR-Media, 2019. (In Russ)]
  11. Окороков А.Н. Неотложная эндокринология. М.: Мед. лит., 2011.[Okorokov A. Emergency Endocrinology. M.: Med. lit., 2011. (In Russ)]
  12. Потемкин В.В., Старостина Е.Г. Неотложная эндокринология. Руководство для врачей. М.: Медицинское информационное агентство, 2008. [Potemkin V., Starostina E. Emergency Endocrinology. A guide for doctors. M.: Medical Information Agency, 2008. (In Russ)]
  13. Becker K.L., Bilezikian J.P., Bremner W.J., et al. Principles & Practice Endocrinology & Metabolism. Lippincott: Williams & Wilkins, 2002.
  14. Hamrahian A.H., Roman S., Milan S., et al. The management of the surgical patient taking glucocorticoids. Edited by UpToDate. Available at: Accessed December 10, 2015.
  15. Периоперационное ведение пациентов с сопутствующими заболеваниями. Руководство для врачей. Под ред. И.Б. Заболотских. М.: Практическая медицина, 2019. [Perioperative management of patients with concomitant diseases. A guide for doctors. Ed. by Zabolotskyh I. M.: Practical medicine, 2019. (In Russ)]
  16. Неотложная эндокринология. Учебное пособие. Л.А. Жукова, С.А. Сумин, Т.Ю. Лебедев и др. М.: Медицинское информационное агентство, 2006. [Emergency endocrinology. Tutorial. Zhukova L., Sumin S., Lebedev T. et al. M.: Medical information agency, 2006. (In Russ)]
  17. Fleisher L.A. Mythen M. Anesthetic implications of concurrent diseases. In: Miller R.D., Eriksson L., Fleisher L., et al. Millerʼs Anesthesia. 8th ed. Vol. 1. Philadelphia: Elsevier Churchill Livingstone, 2015: 1172–1174.
  18. «Анестезия» Рональда Миллера. Под ред. Р. Миллера. Пер. с англ. под общей ред. К.М. Лебединского: в 4 т. СПб.: Человек, 2015. Т. 2. С. 1139–1235. DOI: 10.1097/ALN.0000000000001659. [“Anesthesia” by Ronald Miller. Ed. by Miller R. Translated from English under the general ed. Lebedinsky K.: in 4 vol. SPb.: Human, 2015. Vol. 2. P. 1139–1123. (In Russ)]
  19. Liu M.M., Reidy A.B, Saatee S., Collard C.D. Perioperative steroid management: approaches based on current evidence. Anesthesiology. 2017; 127(1): 166–172. (In Russ)]
  20. Schwartz J.J., Akhtar S., Rosenbaum S.H., et al. Endocrine Function. In: Clinical Anesthesia. Barash P.G., Cullen B.F., Stoelting R.K., et al. 7th ed. Edited by Philadelphia, Wolters Kluwer/Lippincott Williams & Wilkins, 2013: 1137–1138.
  21. Wall R.T. III. Endocrine disease. In: Stoeltingʼs anesthesia and co-existing disease. 7th ed. Hines R., Marschall K. Philadelphia, Saunders/Elsevier, 2017: 449–477.

About efficiency of the pharmacological scores as a predictors of outcomes after cardiac surgery

A.E. Bautin, A.V. Ksendikova, S.S. Belolipetskiy, N.R. Abutalimova, A.O. Marichev, A.V. Naimushin, V.L. Etin, A.M. Radovskiy, L.I. Karpova, V.K. Grebennik, M.L. Gordeev

Almazov National Medical Research Centre, St. Petersburg

For correspondence: Andrei E. Bautin, MD. PhD, Head of research division in anesthesiology and intensive care, Almazov National Medical Research Centre, St. Petersburg; e-mail:, tel. +79217539110

For citation: Bautin AE, Ksendikova AV, Belolipetskiy SS, Abutalimova NR, Marichev AO, Naimushin AV, Etin VL, Radovskiy AM, Karpova LI, Grebennik VK, Gordeev ML. About efficiency of the pharmacological scores as a predictors of outcomes after cardiac surgery. Alexander Saltanov Intensive Care Herald. 2019;2:66–74.

DOI: 10.21320/1818-474X-2019-2-66-74

Pharmacological scores, such as inotropic score (IS) and vasoactive-inotropic score (VIS) were created to quantify doses of vasoactive and inotropic drugs. The number of studies where IS and VIS were used for evaluation of postoperative period of adult patients after cardiac surgery is small.

Objective: to estimate IS and VIS as an approach for monitoring of the hemodynamic profile and clinical outcomes in the early postoperative period of cardiac surgery.

Methods. The study involved 144 patients older than 18 years who underwent cardiac surgery under cardiopulmonary bypass (CPB). In perioperative period we measured cardiac output using a Swan-Ganz catheter with the calculation of central hemodynamic parameters, and also VIS and IS wcre calculated. We evaluated the prognostic value of these pharmacological scores in the development of complications of the early postoperative period, as well as their correlation with the duration of respiratory support, the length of stay in the ICU, and total hospital time.

Results. IS ≥ 10 significantly associated with prolonged respiratory support, a long stay in the ICU and with a mortality rate of 28.6 %. Patients with IS ≥ 10 are characterized by a violation of tissue perfusion, main cause of which may be a low cardiac output syndrome. IS ≥ 10 can be used as criteria for the low cardiac output syndrome with impaired organ perfusion. The use of this pharmacological score as a predictor of adverse clinical outcomes and increased mortality is justified. The hemodynamic profile of patients with VIS ≥ 10 is characterized by the absence of signs of cardiac output decrease and normal organ perfusion. It has low prognostic significance for the adverse postoperative clinical outcomes and should not be used as perioperative criteria for low cardiac output. In addition, VIS ≥ 10 requires careful use as a predictor of adverse postoperative outcomes and mortality.

Keywords: Vasoactive-inotropic score, inotropic score, cardiac surgery, cardiopulmonary bypass, low cardiac output syndrome, vasoplegia syndrome, perioperative period, cardiac anesthesiology

Received: 11.03.2019


  1. Wernovsky G., Wypij D., Jonas R.A., et al. Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants: A comparison of low flow cardiopulmonary bypass and circulatory arrest. Circulation. 1995; 92: 2226–2235.
  2. Maarslet L., Moler M.B., Dall R., et al. Lactate levels predict mortality and need for peritoneal dialysis in children undergoing congenital heart surgery. Acta Anesthesiol. Scand. 2012; 56: 459–64. DOI: 10.1111/j.1399-6576.2011.02588.x
  3. Salvin J.W., Scheurer M.A., Laussen P.C., et al. Factors associated with prolonged recovery after the fontan operation. Circulation. 2008; 118: 171–176. DOI: 10.1161/circulationaha.107.750596
  4. Basaran M., Sever K., Kafali E., et al. Serum lactate level has prognostic significance after pediatric cardiac surgery. Journal of Cardiothoracic and Vascular Anesthesia. 2006; 20(1): 43–44. DOI: 10.1097/
  5. Kulik T.J., Moler F.W., Palmisano J.M., et al. Outcome associated factors in pediatric patients treated with extracorporeal membrane oxygenator after cardiac surgery. Circulation. 1996; 94: II63–II68.
  6. Gaies M.G., Surney J.G., Yen A.H., et al. Vasoactive-inotropic score as a predictor of morbidity and mortality in infants after cardiopulmonary bypass. Pediatric Critical Care Medicine 2010; 11(2): 234–238. DOI: 10.1097/pcc.0b013e3181b806fc
  7. Davidson J., Tong S., Hancock H., et al. Prospective validation of the vasoactive-inotropic score and correlation to short-term outcomes in neonates and infants after cardiothoracic surgery. Intensive Care Med. 2012; 38(7): 1184–1190. DOI: 10.1007/s00134-012-2544-x
  8. Butts R.J., Scheurer M.A., Altz A.M., et al. Comparison of maximum vasoactive inotropic score and low cardiac output syndrome as markers of early postoperative outcomes after neonatal cardiac surgery. Pediatr. Cardiol. 2012; 33(4): 633–638. DOI: 10.1007/s00246-012-0193-z
  9. Sanil Y., Aggarwal S. Vasoactive-inotropic score after pediatric heart transplant: A marker of adverse outcome. Pediatr. Transplant. 2013; 17(6): 567–572. DOI: 10.1111/petr.12112
  10. Nguyen H.V., Havalad V., Aponte-Patel L., et al. Temporary biventricular pacing decreases the vasoactive-inotropic score after cardiac surgery: a substudy of a randomized clinical trial. J. Thorac. Cardiovasc. Surg. 2013; 146(2): 296–301. DOI: 10.1016/j.jtcvs.2012.07.020
  11. Landoni G., Lomivorotov V.V., Alvaro G., et al. Levosimendan for Hemodynamic Support after Cardiac Surgery. The New England Journal of Medicine. 2017; 376(21): 2021–2031. DOI: 10.1056/NEJMoa1616325
  12. Козлов И.А., Кричевский Л.А. Оценка эффективности левосимендана в кардиохирургии. Вестник анестезиологии и реаниматологии. 2017; 14(4): 81–82. DOI: 10.21292/2078-5658-2017-14-4-81-82. [Kozlov I.A., Krichevskiy L.A. Evaluation of levosimedan efficiency in cardiac surgery. Messenger of anethesiology and resuscitation. 2017; 14(4): 81–82. DOI: 10.21292/2078-5658-2017-14-4-81-82. (In Russ)]

Therapeutic hypothermia in treatment of different cerebral injuries

A.V. Butrov1, B.D. Torosyan1, D.V. Cheboksarov1,2, G.R. Makhmutova1,2

1 Peoples Friendship University of Russia (RUDN University), Moscow

2 Moscow City clinical hospital named author V.V. Vinogradov, Moscow

For correspondence: Andrey V. Butrov, DSci, Professor, department of anaestesiology and reanimatology with clinical rehabilitation course RUDN University, Moscow; e-mail:

For citation: Butrov AV, Torosyan BD, Cheboksarov DV, Makhmutova GR. Therapeutic hypothermia in treatment of different cerebral injuries. Alexander Saltanov Intensive Care Herald. 2019;2:75-81.

DOI: 10.21320/1818-474X-2019-2-75-81

There is an increasing incidence of various cerebral eventsin Russia, as well as throughout the world. At the same time, despite of all the successes of modern medicine, the treatment outcomes of these patient groups haven’t improved. The main successes are based on faster patient delivery to hospitals and on the creation of specialized centers for this cohort of patients. At the same time, the effectiveness of pharmacological agents with neuroprotective activity is questionable. On the other hand, therapeutic hypothermia techniques have proven to be an effective method of neuroprotection in various cerebral events. These methods can be divided into local and general hypothermia. Each of these options has its own advantages and indications. Thus, the use of general hypothermia techniques maintains the target temperature of the whole body, these techniques are more controllable, but at the same time, the methods of local craniocerebral hypothermia allows to affect the target organ. The methods of hypothermia and thermostabilization have been proven to improve the treatment results of patients post-CPR and in children with neonatal hypoxia. The effectiveness of hypothermia in the remaining pathological conditions of the brain has not yet been investigated. Studies of the last 5 years have not revealed high efficacy of general hypothermia at TBI, so almost of all studies indicated that normothermia and hypothermia are equally effective. Studies are ongoing in patients with subarachnoid hemorrhage, subdural hematomas and ischemic stroke. Identifying groups of patients who are recommended for these methods for complex treatment can lead to progress in improving survival and neurological outcome.

Keywords: therapeutic hypothermia, craniocerebral hypothermia, traumatic brain injury, cerebral infarction, subarachnoid hemorrhage, cerebral hemorrhage

Received: 04.02.2019


  1. 01_Заболеваемость всего населения России в 2017 году [электронный документ]. Доступно по: Ссылка активна на 20.01.2019. [Zabolevaemost’ vsego naseleniya Rossii v 2017 godu [Internet] Available from: (accessed 20.01.2019). (In Russ)]
  2. Simon D.J., Weimer R.M., McLaughlin T., et al. Caspase Cascade Regulating Developmental Axon Degeneration. Journal of Neuroscience, 2012 5; 32(49): 17540–17553. DOI: 10.1523/jneurosci.3012–12.2012
  3. Усенко Л.В., Царев А.В. Искусственная гипотермия в современной реаниматологии. Общая реаниматология. 2009; 5(1): 21–23. DOI: 10.15360/1813-9779-2009-1-21 [Usenko L.V., Carev A.V. Iskusstvennaya gipotermiya v sovremennoy reanimatologii. Obshaya reanimatologiya. 2009; 5(1): 21–23. DOI: 10.15360/1813-9779-2009-1-21. (In Russ)]
  4. MacLellan C.L., Davies L.M., Fingas M.S., Colbourne F. The influence of hypothermia on outcome after intracerebral hemorrhage in rats. Stroke; 2006; 37(5): 1266–1270. DOI: 10.1161/01.STR.0000217268.81963.78
  5. Lazzaro M.A., Prabhakaran S. Induced hypothermia in acute ischemic stroke. Expert Opin. Investig. Drugs, 2008; 17(8): 1161–1174. DOI: 10.1517/13543784.17.8.1161
  6. Keller E., Imhof H.G., Gasser S., et al. Endovascular cooling with heat exchange catheters: a new method to induce and maintain hypothermia. Intensive Care Med., 2003; 29(6): 939–943. DOI: 10.1007/s00134-003-1685-3
  7. Guluma K.Z., Hemmen T.M., Olsen S.E., Rapp K.S., Lyden P.D. A trial of therapeutic hypothermia via endovascular approach in awake patients with acute ischemic stroke: methodology. Acad. Emerg. Med., 2006; 13(8): 820–827.
  8. Van der Worp H.B., Macleod M.R., Kollmar R. Therapeutic hypothermia for acute ischemic stroke: ready to start large randomized trials. J. Cereb. Blood Flow Metab., 2010; 30(6): 1079–1093. DOI: 10.1038/jcbfm.2010.44
  9. Qiu W., Shen H., Zhang Y., Wang W., et al. Noninvasive selective brain cooling by head and neck cooling is protective in severe traumatic brain injury. J. Clin. Neurosci. 2006; 13(10): 995–1000.
  10. Lazzaro M.A., Prabhakaran S. Induced hypothermia in acute ischemic stroke. Expert Opin. Investig. Drugs, 2008; 17(8): 1161–1174. DOI: 10.1517/13543784.17.8.1161
  11. Kallmünzer B., Krause C., Pauli E., et al. Standardized antipyretic treatment in stroke: a pilot study. Cerebrovasc. Dis. 2011; 31(4): 382–389. DOI: 10.1159/000321733
  12. Guluma K.Z., Oh H., Yu S.W., et al. Effect of endovascular hypothermia on acute ischemic edema: morphometric analysis of the ICTuS trial. Neurocrit. Care, 2008; 8(1): 42–47.
  13. Mayer S.A., Kowalski R.G., Presciutti M., et al. Clinical trial of a novel surface cooling system for fever control in neurocritical care patients. Crit. Care Med. 2004; 32: 2508–2515.
  14. Qiu W., Shen H., Zhang Y., et al. Noninvasive selective brain cooling by head and neck cooling is protective in severe traumatic brain injury. J. Clin. Neurosci. 2006; 13(10): 995–1000.
  15. Wang H., Olivero W., Lanzino G., et al. Rapid and selective cerebral hypothermia achieved using a cooling helmet. J. Neurosurg. 2004; 100(2): 272–277.
  16. Harms H., Prass K., Meisel C.,et al. Preventive antibacterial therapy in acute ischemic stroke: a randomized controlled trial. PLoS One. 2008; 3(5): e2158. DOI: 10.1371/journal.pone.0002158
  17. Chen J., Ji X., Ding Y., et al. A novel approach to reduce hemorrhagic transformation after interventional management of acute stroke: catheter-based selective hypothermia. Med. Hypotheses, 2009; 72(1): 62–63. DOI: 10.1016/j.mehy.2008.07.056
  18. Keller E., Mudra R., Gugl C., et al. Theoretical evaluations of therapeutic systemic and local cerebral hypothermia. J. Neurosci Methods. 2009; 178(2): 345–349. DOI: 10.1016/j.jneumeth.2008.12.030
  19. Бутров А.В., Шевелев О.А., Петрова М.В. и др. «АТГ-01 (аппарат терапевтической гипотермии — 01)» у больных в критических состояниях: учебное пособие. М.: Медиамед, 2014. [Butrov A.V., ShevelevO.A., PetrovaM.V., et al. “ATG-01 (apparat terapevticheskoy gipotermii — 01)” ubolnikh v kriticheskikh sostoyaniyakh: uchebnoyeposobiye. M.: Mediamed, 2014. (In Russ)]
  20. Polderman K.H. Mechanisms of action, physiological effects, and complications of hypothermia. Crit. Care Med. 2009; 37(7 Suppl.): S186–S202. DOI: 10.1097/CCM.0b013e3181aa5241
  21. Van der Worp H.B., Sena E.S., Donnan G.A., et al. Hypotermia in animal models of acute ishaemic stroke: a systematic review and meta-analysis. Brain. 2007; 130(Pt 12): 3063–3074.
  22. Faridar A., Bershad E.M., Emiru T., et al. Therapeutic hypothermia in stroke and traumatic brain injury. Front. Neurol. 2011; 27(2): 80. DOI: 10.3389/fneur.2011.00080
  23. Каленова И.Е., Шаринова И.А., Шевелев О.А., Бутров А.В. Опыт применения терапевтической гипотермии в лечении ишемического инсульта. Неврология, нейропсихиатрия, психосоматика. 2012; 2: 41–45. DOI: 10.14412/2074-2711-2012-380 [Kalenova I.E., Sharinova I.A., Shevelev O.A., Butrov A.V. Opit primeneniya terapevticheskoy gipotermii v lechenii ishemicheskogo insulta. Nevrologiya, neyropsikhiatriya, psikhosomatika. 2012; 2: 41–45. (In Russ)]
  24. Абудеев С.А., Попугаев К.А., Кругляков Н.М. и др. Влияние гипотермии на напряжение кислорода в паренхиме головного мозга при аневризматическом субарахноидальном кровоизлиянии. Анестезиология и реаниматология. 2016; 61(2): 155–158. DOI: 10.18821/0201-7563-2016-61-2-155-158 [Abudeev S.A., Popugev K.A., Kruglyakov N.M., et al. Vliyaniye gipotermii na napryajeniye kisloroda v parenkhime golovnogo mozga pri anevrizmaticheskom subarakhnoidalnom kroovoizliyanii. Anesteziologiya I reanimatologiya. 2016; 61(2): 155–158. (In Russ)]
  25. Prasad K., Krishnan P.R. Fever is associated with doubling of odds of short-term mortality in ischemic stroke: an updated meta-analysis. Acta Neurol. Scand., 2010; 122(6): 404–408. DOI: 10.1111/j.1600-0404.2010.01326.x
  26. Broessner G., Beer R., Lackner P., et al. Endovascularly based, long-term normothermia in ICU patients with cerebrovascular disease. Stroke. 2009; 40(12): e657–e665. DOI: 10.1161/STROKEAHA.109.557652
  27. Lazzaro M.A., Prabhakaran S. Induced hypothermia in acute ischemic stroke. Expert Opin. Investig. Drugs. 2008; 17(8): 1161–1174. DOI: 10.1517/13543784.17.8.1161
  28. Pastukhov A., Krisanova N., Maksymenko V., Borisova T. Personalized approach in brain protection by hypothermia: individual changes in non-pathological and ischemia-related glutamate transport in brain nerve terminals. EPMA J. 2016; 7: 26. DOI: 10.1186/s13167-016-0075-1
  29. Hua C., Ju W., Jin H., et al. Molecular chaperones and hypoxic-ischemic encephalopathy. Neural. Regen. Res. 2017; 12(1): 153–160. DOI: 10.4103/1673–5374.199008
  30. Giraud R., Siegenthaler N., Bendjelid K. Cardiac index during therapeutic hypothermia: which target value is optimal? Crit. Care. 2013; 17(2): 214. DOI: 10.1186/cc12523
  31. Bergman R., van Zanten A.R., et al. Haemodynamic consequences of mild therapeutic hypothermia after cardiac arrest. Eur. J. Anaesthesiol. 2010; 27(4): 383–387. DOI: 10.1097/EJA.0b013e3283333a7d
  32. Arabi Y.M., Casaer M.P., Chapman M., et al. The intensive care medicine research agenda in nutrition and metabolism. Intensive Care Med. 2017; 43(9): 1239–1256. DOI: 10.1007/s00134-017-4711-6
  33. Bergman R., van Zanten A.R., et al. Haemodynamic consequences of mild therapeutic hypothermia after cardiac arrest. Eur. J. Anaesthesiol. 2010; 27(4): 383–387. DOI: 10.1097/EJA.0b013e3283333a7d
  34. Leslie K., Bjorksten A.R., Ugoni A., Mitchell P. Mild core hypothermia and anesthetic requirement for loss of responsiveness during propofol anesthesia for craniotomy. Anesth. Analg., 2002; 94(5): 1298–1303.
  35. Martinello K., Hart A.R., Yap S., Mitra S., Robertson N.J. Management and investigation of neonatal encephalopathy: 2017 update. Arch. Dis. Child Fetal. Neonatal. Ed. 2017; 102(4): F346–F358. DOI: 10.1136/archdischild-2015-309639
  36. Perkins G.D., Olasveengen T.M., Maconochie I., et al. European Resuscitation Council Guidelines for Resuscitation: 2017 update. Resuscitation. 2018; 123: 43–50. DOI: 10.1016/j.resuscitation.2017.12.007
  37. Moler F.W., Silverstein F.S., Holubkov R., et al. THAPCA Trial Investigators. Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children. N. Engl. J. Med., 2017; 376(4): 318–329. DOI: 10.1056/NEJMoa1610493
  38. Crompton E.M., Lubomirova I., Cotlarciuc I., et al. Meta-Analysis of Therapeutic Hypothermia for Traumatic Brain Injury in Adult and Pediatric Patients. Crit. Care Med., 2017; 45(4): 575–583. DOI: 10.1097/CCM.0000000000002205
  39. Puccio A.M., Fischer M.R., Jankowitz B.T.,et al. Induced normothermia attenuates intracranial hypertension and reduces fever burden after severe traumatic brain injury. Neurocrit. Care, 2009; 11(1): 82–87. DOI: 10.1007/s12028-009-9213-0
  40. Sydenham E., Roberts I., Alderson P. Hypothermia for traumatic head injury. Cochrane Database Syst. Rev. 2017; 9: CD001048. DOI: 10.1002/14651858.CD001048
  41. Cooper D.J., Nichol A.D., Bailey M., et al. POLAR Trial Investigators and the ANZICS Clinical Trials Group. Effect of Early Sustained Prophylactic Hypothermia on Neurologic Outcomes Among Patients With Severe Traumatic Brain Injury: The POLAR Randomized Clinical Trial. JAMA. 2018; 320(21): 2211–2220. DOI: 10.1001/jama.2018.17075
  42. Shoji Y., Hiroyuki Y. Targeted temperature management in traumatic brain injury. J. Intensive Care, 2016; 4: 28. DOI: 10.1186/s40560-016-0137-4
  43. Broderick J., Connolly S., Feldmann E., et al., American Heart Association/American Stroke Association Stroke Council; American Heart Association/American Stroke Association. High Blood Pressure Research Council. Quality of Care and Outcomes in Research Interdisciplinary Working Group. Circulation. 2007; 116(16): e391–e413.
  44. Zazulia A.R., Diringer M.N., Derdeyn C.P., Powers W.J. Progression of mass effect after intracerebral hemorrhage. Stroke. 1999; 30(6): 1167–1173.
  45. Venkatasubramanian C., Mlynash M., Finley-Caulfield A., et al. Natural History of Perihematomal Edema After Intracerebral Hemorrhage Measured by Serial Magnetic Resonance Imaging. Stroke. 2011; 42(1): 73–80. DOI: 10.1161/strokeaha.110.590646
  46. MacLellan C.L., Davies L.M., Fingas M.S., Colbourne F. The influence of hypothermia on outcome after intracerebral hemorrhage in rats. Stroke. 2006; 37(5): 1266–1270.
  47. Gasser S., Khan N., Yonekawa Y., et al. Long-term hypothermia in patients with severe brain edema after poor-grade subarachnoid hemorrhage: feasibility and intensive care complications. J. Neurosurg. Anesthesiol. 2003; 15(3): 240–248.
  48. Kollmar R., Schellinger P.D., Steigleder T., et al. Ice-cold saline for the induction of mild hypothermia in patients with acute ischemic stroke: a pilot stud. Stroke. 2009; 40(5): 1907–1909. DOI: 10.1161/strokeaha.108.530410
  49. Georgiadis D., Schwarz S., Kollmar R., Schwab S. Endovascular cooling for moderate hypothermia in patients with acute stroke: first results of a novel approach. Stroke. 2009; 40(5): 1907–1909.
  50. Торосян Б.Д., Бутров А.В., Шевелев О.А. и др. Краниоцеребральная гипотермия — эффективное средство нейропротекции у пациентов с инфарктом мозга. Анестезиология и реаниматология, 2018; 3: 58–63. DOI: 10.17116/anaesthesiology201803158 [Torosyan B.D., Butrov A.V., Shevelev O.A., et al. Kraniocerebralnaya gipotermiya — effektivnoe sredstvo neyroprotekcii u pacientov s infarktom mozga. Anesteziologiya i reanimatologiya. 2018; 3: 58–63. (In Russ)]
  51. Winkel P., Bath P.M., Gluud C., et al. EuroHYP-1 trial investigators. Statistical analysis plan for the EuroHYP-1 trial: European multicentre, randomised, phase III clinical trial of the therapeutic hypothermia plus best medical treatment versus best medical treatment alone for acute ischaemic stroke. 2017; 18(1): 573. DOI: 10.1186/s13063-017-2302-z

Hypophosphatemia and refeeding syndrome in the resumption of nutrition in critical care patients (review)

A.I. Yaroshetskiy1,2, V.D. Konanykhin1, S.O. Stepanova2, N.A. Rezepov2

1 Pirogov Russian National Research Medical University, Moscow

2 L.A. Vorokhobov Municipal Clinical Hospital No. 67, Moscow

For correspondence: Vasily D. Konanykhin, laboratory assistant of the Department of Anesthesiology and Critical Care of the Scientific Research Institute for Clinical Surgery at N.I. Pirogov Russian National Research Medical University; e-mail:

For citation: Yaroshetskiy AI, Konanykhin VD, Stepanova SO, Rezepov NA. Hypophosphatemia and refeeding syndrome in the resumption of nutrition in critical care patients (review). Alexander Saltanov Intensive Care Herald. 2019;2:82–91.

DOI: 10.21320/1818-474X-2019-2-82-91

Refeeding syndrome is a life-threatening condition that occurs when nutrition is restarted in patients with initial malnutrition. For the first time refeeding syndrome was described more than 70 years ago but it still has not been studied enough. The pathophysiology of refeeding syndrome is based on severe electrolyte and metabolic disorders caused by the restoration of nutrition with an initial deficiency of phosphorus, potassium, magnesium which lead to organ failure. Hypophosphatemia is the main feature of the refeeding syndrome while in ICU patients there are many other causes of hypophosphatemia which complicates diagnostics. Most studies on refeeding syndrome have been conducted among patients with anorexia nervosa. In ICU refeeding hypophosphatemia occurs in about 34 % of cases but until recently all guidelines for the management of this condition have been extrapolated from the practice of treatment anorexia nervosa and were based on expert opinion. Several major studies have proven the effectiveness of a hypocaloric feeding during refeeding syndrome in critically ill patients recently.

This review is devoted to the problem of refeeding syndrome in patients with anorexia nervosa and critical care patients, differential diagnostics and treatment approaches for this condition.

Keywords: refeeding syndrome, hypophosphatemia, nutritional support, parenteral nutrition

Received: 03.03.2019


  1. Solomon S.M., Kirby D.F. The refeeding syndrome: A review. J. Parenter. Enter. Nutr. 1990; 14(1): 90–97. DOI: 10.1177/014860719001400190
  2. Schnitker M.A., Mattman P.E., Bliss T.L. A clinical study of malnutrition in Japanese prisoners of war. Ann. Intern. Med. 1951; 35(1): 69–96.
  3. Weinsier R.L., Krumdieck C.L. Death resulting from overzealous total parenteral nutrition: the refeeding syndrome revisited. Am. J. Clin. Nutr. 1981; 34(3): 393–399. DOI: 10.1093/ajcn/34.3.393
  4. Skipper A. Refeeding syndrome or refeeding hypophosphatemia: A systematic review of cases. Nutr. Clin. Pract. 2012; 27(1): 34–40. DOI: 10.1177/0884533611427916
  5. Fuentes E., Yeh D.D., Quraishi S.A., et al. Hypophosphatemia in Enterally Fed Patients in the Surgical Intensive Care Unit. Nutr. Clin. Pract. 2017; 32(2): 252–257. DOI: 10.1177/0884533616662988
  6. Doig G.S., Simpson F., Heighes P.T., et al. Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial. Lancet Respir. Med. 2015; 3(12): 943–952.
  7. Olthof L.E., Koekkoek W., van Setten C., et al. Impact of caloric intake in critically ill patients with, and without, refeeding syndrome: A retrospective study. Clin. Nutr. 2018; 37(5): 1609–1617. DOI: 10.1016/j.clnu.2017.08.001
  8. Crook M.A. Refeeding syndrome: Problems with definition and management. Nutrition. 2014; 30(11–12): 1448–1455. DOI: 10.1016/j.nut.2014.03.026
  9. Byrnes M.C., Stangenes J. Refeeding in the ICU: An adult and pediatric problem. Curr. Opin. Clin. Nutr. Metab. Care. 2011; 14(2): 186–192. DOI: 10.1097/MCO.0b013e328341ed93
  10. Rio A., Whelan K., Goff L., et al. Occurrence of refeeding syndrome in adults started on artificial nutrition support: Prospective cohort study. BMJ Open. 2013; 3(1): 1–10. DOI: 10.1136/bmjopen-2012-002173
  11. Suzuki S., Egi M., Schneider A.G., et al. Hypophosphatemia in critically ill patients. J. Crit. Care. 2013; 28(4): 536.e9–536.e19. DOI: 10.1016/j.jcrc.2012.10.011
  12. Golden N.H., Keane-Miller C., Sainani K.L., et al. Higher caloric intake in hospitalized adolescents with anorexia nervosa is associated with reduced length of stay and no increased rate of refeeding syndrome. J. Adolesc. Heal. 2013: 573–578. DOI: 10.1016/j.jadohealth.2013.05.014
  13. Coskun R., Gundogan K., Baldane S., et al. Refeeding hypophosphatemia: a potentially fatal danger in the intensive care unit. Turkish J. Med. Sci. 2014; 44(3): 369–374.
  14. Nutrition support for adults: oral nutrition support, enteral tube feeding and parenteral nutrition. Guidance and guidelines. NICE. 2006.
  15. Elia M., British Association for Parenteral and Enteral Nutrition. The “MUST” report: nutritional screening of adults: a multidisciplinary responsibility: development and use of the “malnutrition universal screening tool” (‘MUST’) for adults. BAPEN. 2003.
  16. Reilly H.M., Martineau J.K., Moran A., et al. Nutritional screening — evaluation and implementation of a simple Nutrition Risk Score. Clin. Nutr. 1995; 14(5): 269–273.
  17. Elnenaei M.O., Alaghband-Zadeh J., Sherwood R., et al. Leptin and insulin growth factor 1: diagnostic markers of the refeeding syndrome and mortality. Br. J. Nutr. 2011; 106(06): 906–912. DOI: 10.1017/S0007114511001097
  18. Whitelaw M., Gilbertson H., Lam P.Y., et al. Does Aggressive Refeeding in Hospitalized Adolescents With Anorexia Nervosa Result in Increased Hypophosphatemia? J. Adolesc. Heal. 2010; 46(6): 577–582. DOI: 10.1016/j.jadohealth.2009.11.207
  19. Redgrave G.W., Leonpacher A.K., Pletch A., et al. Refeeding and weight restoration outcomes in anorexia nervosa: Challenging current guidelines. Int. J. Eat Disord. 2015; 48(7): 866–873. DOI: 10.1002/eat.22390
  20. Ornstein R.M., Golden N.H., Jacobson M.S., et al. Hypophosphatemia during nutritional rehabilitation in anorexia nervosa: implications for refeeding and monitoring. J. Adolesc. Health. 2003; 32(1): 83–88.
  21. Cahill G.F. Starvation in Man. N. Engl. J. Med. 1970; 282(12): 668–675. DOI: 10.1056/NEJM197003192821209
  22. Cahill G.F., Owen O.E., Owen O.E. Starvation and survival. Trans. Am. Clin. Climatol. Assoc. American Clinical and Climatological Association. 1968; 79: 13–20.
  23. Cuthbertson D. Post-shock metabolic response. Lancet. Elsevier. 1942; 239(6189): 433–437. DOI: 10.1016/S0140–6736(00)79605-X
  24. Boateng A.A., Sriram K., Meguid M.M., et al. Refeeding syndrome: Treatment considerations based on collective analysis of literature case reports. Nutrition. 2010; 26(2): 156–167. DOI: 10.1016/j.nut.2009.11.017
  25. Marinella M.A. Refeeding syndrome and hypophosphatemia. J. Intensive Care Med. 2005; 20(3): 155–159. DOI: 10.1177/0885066605275326
  26. Obeid O.A., Hachem D.H., Ayoub J.J. Refeeding and metabolic syndromes: two sides of the same coin. Nutr Diabetes. Nature Publishing Group. 2014; 4(6): e120. DOI: 10.1038/nutd.2014.21
  27. Mehanna H.M., Moledina J., Travis J. Refeeding syndrome: what it is, and how to prevent and treat it. BMJ. BMJ Publishing Group. 2008; 336(7659): 1495–1498. DOI: 10.1136/bmj.a301
  28. Ярошецкий А.И., Васильева С.О., Резепов Н.А. и др. Применение непрямой калориметрии для оценки метаболизма глюкозы и липидов при проведении полного парентерального питания у хирургических пациентов: пилотное исследование. Вестник интенсивной терапии. 2016; 4: 12–18.[Yaroshetskii A.I., Vasilʼeva S.O., Rezepov N.A., et al. Primenenie nepryamoi kalorimetrii dlya otsenki metabolizma glyukozy i lipidov pri provedenii polnogo parenteralʼnogo pitaniya u khirurgicheskikh patsientov: pilotnoe issledovanie. (The use of indirect calorimetry to assess glucose and lipid metabolism during full parenteral nutrition in surgical patients: a pilot study.) Vestnik intensivnoi terapii. 2016; 4: 12–18. (In Russ)]
  29. Kavanagh B.P., McCowen K.C. Glycemic Control in the ICU. N. Engl. J. Med.. 2010; 363(26): 2540–2546. DOI: 10.1056/NEJMcp1001115
  30. Ярошецкий А.И., Резепов Н.А., Васильева С.О. и др. Выбор автоматизированного или «ручного» управления гликемией при проведении полного парентерального питания в хирургии: сравнительное исследование. Анналы хирургии. 2015; 2: 31–40.[Yaroshetskii A.I., Rezepov N.A., Vasilʼeva S.O., et al. Vybor avtomatizirovannogo ili “ruchnogo” upravleniya glikemiei pri provedenii polnogo parenteralʼnogo pitaniya v khirurgii: sravnitelʼnoe issledovanie.(Selection of automated or “manual” glycemic control during full parenteral nutrition in surgery: a comparative study.) Annaly khirurgii. 2015; 2: 31–40. (In Russ)]
  31. Lee J.W. Fluid and electrolyte disturbances in critically ill patients. Electrolyte Blood Press. Korean Society of Electrolyte Metabolism. 2010; 8(2): 72–81. DOI: 10.5049/EBP.2010.8.2.72
  32. Hessels L., Mijzen L.J., Hoekstra M., et al. The relationship between serum potassium, potassium variability and in-hospital mortality in critically ill patients and a before-after analysis on the impact of computer-assisted potassium control. Crit. Care. 2015; 19(1): 4. DOI: 10.1186/s13054-014-0720-9
  33. Barbosa E.B., Tomasi C.D., de Castro Damasio D., et al. Effects of magnesium supplementation on the incidence of acute kidney injury in critically ill patients presenting with hypomagnesemia. Intensive Care Med. 2016; 42(6): 1084–1085. DOI: 10.1007/s00134-016-4276-9
  34. Collie J.T.B., Greaves R.F., Jones O.A.H., et al. Vitamin B1 in critically ill patients: needs and challenges. Clin. Chem. Lab. Med. 2017; 55(11): 1652–1668. DOI: 10.1515/cclm-2017-0054
  35. Van Snippenburg W., Reijnders M.G.J., Hofhuis J.G.M., et al. Thiamine Levels During Intensive Insulin Therapy in Critically Ill Patients. J. Intensive Care Med. 2017; 32(9): 559–564. DOI: 10.1177/0885066616659429
  36. Halevy J., Bulvik S. Severe hypophosphatemia in hospitalized patients. Arch. Intern. Med. 1988; 148(1): 153–155.
  37. Robinson P., Rhys Jones W. MARSIPAN: management of really sick patients with anorexia nervosa. BJPsych. Adv. 2018; 24(01): 20–32. DOI: 10.1192/bja.2017.2
  38. Bargiacchi A., Clarke J., Paulsen A., et al. Refeeding in anorexia nervosa. Eur. J. Pediatr. European Journal of Pediatrics; 2018; DOI: 10.1007/s00431-018-3295-7
  39. Rhoads J.E., Vars H.M., Dudrick S.J. The Development of Intravenous Hyperalimentation. Surg. Clin. North. Am. Elsevier. 1981; 61(3): 429–435. DOI: 10.1016/S0039–6109(16)42429–1
  40. Copeland E.M., Macfayden B.V., Dudrick S.J. Intravenous hyperalimentation in cancer patients. J. Surg. Res. 1974; 16(3): 241–247.
  41. Dudrick S.J., Macfadyen B.V., Van Buren C.T., et al. Parenteral hyperalimentation. Metabolic problems and solutions. Ann. Surg. Lippincott, Williams, and Wilkins. 1972; 176(3): 259–264.
  42. Energy-Dense versus Routine Enteral Nutrition in the Critically Ill. N. Engl. J. Med. 2018; 379(19): 1823–1834. DOI: 10.1056/nejmoa1811687
  43. Rice T.W., Wheeler A.P., Thompson B.T., et al. Initial Trophic vs Full Enteral Feeding in Patients With Acute Lung Injury: The EDEN Randomized Trial. JAMA J. Am. Med. Assoc. 2012; 307(8): 795–803. DOI: 10.1001/jama.2012.137
  44. Shen T., Braude S. Changes in serum phosphate during treatment of diabetic ketoacidosis: predictive significance of severity of acidosis on presentation. Intern. Med. J. 2012; 42(12): 1347–1350. DOI: 10.1111/imj.12001
  45. Arabi Y.M., Haddad S.H., Tamim H.M., et al. Near-Target Caloric Intake in Critically Ill Medical-Surgical Patients Is Associated With Adverse Outcomes. J. Parenter Enter Nutr. 2010; 34(3): 280–288. DOI: 10.1177/0148607109353439
  46. Arabi Y., Al-Dorzi H., Jones G., et al. Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults Statin View project Saudi Clinical Practice Guidelines View project. 2015; 1–11. DOI: 10.1056/NEJMoa1502826
  47. Garber A.K. A few steps closer to answering the unanswered questions about higher calorie refeeding. J. Eat Disord. Journal of Eating Disorders. 2017; 5(1): 4–6. DOI: 10.1186/s40337-017-0139-1
  48. Лейдерман И.Н., Ярошецкий А.И., Е.А. Кокарев, В.А. Мазурок. Парентеральное питание: вопросы и ответы. Руководство для врачей. Санкт-Петербург: Онли-Пресс, 2016.[Leiderman I.N., Yaroshetskii A.I., E.A. Kokarev, V.A. Mazurok. Parenteralʼnoe pitanie: voprosy i otvety: rukovodstvo dlya vrachei. (Parenteral nutrition: questions and answers. A guide for physicians.) Sankt-Peterburg: Onli-Press Publ., 2016. (In Russ)]
  49. Lund B.C., Hernandez E.R., Yates W.R., et al. Rate of inpatient weight restoration predicts outcome in anorexia nervosa. Int. J. Eat. Disord. 2009; 42(4): 301–305. DOI: 10.1002/eat.20634
  50. Cockfield A. and Philpot U. Re-feeding protocol for seriously ill patients with anorexia nervosa. The British dietic association. Birmingham, 2011.
  51. Гельфанд Б.Р., Ярошецкий А.И., Мамонтова О.А. и др. Безопасность парентерального питания в хирургии и интенсивной терапии: вопросы и ответы. Анналы хирургии. 2012; 4: 5–11.[Gelʼfand B.R., Yaroshetskii A.I., Mamontova O.A., et al. Bezopasnostʼ parenteralʼnogo pitaniya v khirurgii i intensivnoi terapii:voprosy i otvety.(Safety of parenteral nutrition in surgery and intensive care: questions and answers.) Annaly khirurgii. 2012; 4: 5–11. (In Russ)]
  52. Garber A.K., Mauldin K., Michihata N., et al. Higher calorie diets increase rate of weight gain and shorten hospital stay in hospitalized adolescents with anorexia nervosa. J. Adolesc. Heal. 2013; 53(5): 579–584. DOI: 10.1016/j.jadohealth.2013.07.014
  53. Dalle Grave R., El Ghoch M., Milanese C., et al. Body composition, eating disorder psychopathology, and psychological distress in anorexia nervosa: a longitudinal study. Am. J. Clin. Nutr. 2014; 99(4): 771–778. DOI: 10.3945/ajcn.113.078816
  54. Gaudiani J.L., Sabel A.L., Mascolo M., et al. Severe anorexia nervosa: Outcomes from a medical stabilization unit. Int. J. Eat. Disord. 2012; 45(1): 85–92. DOI: 10.1002/eat.20889
  55. Sabel A.L., Catanach B., Rylander M., et al. Medical outcomes for adults hospitalized with severe anorexia nervosa: An analysis by age group. Int. J. Eat. Disord. 2015; 49(4): 378–385. DOI: 10.1002/eat.22437
  56. Boot R., Koekkoek K., van Zanten A.R.H. Refeeding syndrome: Relevance for the critically ill patient. Curr. Opin. Crit. Care. 2018; 24(4): 235–240. DOI: 10.1097/MCC.0000000000000514
  57. Singer P., et al. ESPEN guideline on clinical nutrition in the intensive care unit. Clinical Nutrition (2018). https://
  58. Fraipont V., Preiser J. Energy Estimation and Measurement in Critically Ill Patients. Journal of Parenteral and Enteral Nutrition. 2013; 37(6): 705–713. DOI: 10.1177/0148607113505868
  59. Weijs P.J.M., Looijaard W.G., Beishuizen A., et al. Early high protein intake is associated with low mortality and energy overfeeding with high mortality in non-septic mechanically ventilated critically ill patients. Crit. Care. 2014; 18(6): 701. DOI: 10.1186/s13054-014-0701-z
  60. Arabi Y., Aldawood A., Haddad S., et al. Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults. N. Engl. J. Med. 2015; 372(25): 2398–2408. DOI: 10.1056/NEJMoa1502826

Intraoperative intravenous lidocaine for prevention of chronic pain syndrome

Ya.I. Vasilev, N.G. Marova, A.E. Karelov, P.A. Grib, N.A. Timofeev

North-Western State Medical University named after I.I. Mechnikov, St. Petersburg

For correspondence: Yaroslav I. Vasilev, associate professor Vladimir L. Vanevskii anaesthesiology and reanimatology Department of North-Western State Medical University named after I.I. Mechnikov, St. Petersburg; e-mail:,

For citation: Vasilev YaI, Marova NG, Karelov AE, Grib PA, Timofeev NA. Intraoperative intravenous lidocaine for prevention of chronic pain syndrome. Alexander Saltanov Intensive Care Herald. 2019;2:92-97.

DOI: 10.21320/1818-474X-2019-2-92-97

Chronic pain after a laparoscopic cholecystectomia represents a considerable problem. One of the directions of prevention and treatment of a chronic pain syndrome are attempts of use of various adjuvants from which the most promising results showed antidepressants, antikonvulsant, antagonists of NMDA of receptors, α2-агонисты and local anesthetics.

The purpose of this single center randomized, and placebo-controlled study was to evaluate the impact of IV lidocaine on CPPS (Chronic Postoperative Pain Syndrome).

Materials and Methods. Following approval of the study protocol by the University ethics committee 96 patients were randomized into 2 groups for participation in this study. All patients were ASA class II and III, aged 21 years and older and undergoing elective laparoscopic cholecystectomy under general anesthesia. All patients were randomly allocated into 2 groups of equal size to receive either lidocaine infusion (Lidocaine group), or 0.9 % sodium chloride infusion (Control group).

Results. The incidence of CPPS after 3 months was significantly lower in the Lidocaine group than in the Control group (10 vs 37,3 %, Fisher’s Exact Test P = 0.0069) with an overall incidence of 29.2 %, and after 6 months 18.3 % (16 vs 19.3 % accordingly, Fisher’s Exact Test P = 1.0). Date evaluation of PRI NWC (total and in each of 3 category) 6 month and 12 month after surgery with Fisher’s Exact Test and t Mann Whitney test, could not find any difference in groups.

Conclusion. No differences between control group and lidocaine in 6 and 12 months were found after surgery.

Keywords: Chronic Postoperative Pain Syndrome, CPPS chronic pain, prevention of chronic pain, lidocaine, adjuvants for CPPS treatment, intraoperative administration of lidocaine

Received: 31.01.2019


  1. Macrae W.A. Chronic pain after surgery. Br. J. Anaesth. 2001; 87: 88–98. DOI: org/10.1093/bja/87.1.88
  2. Овечкин А.М. Хроническая послеоперационная боль — масштаб проблемы и способы профилактики. Российский журнал боли. 2016; 1: 3–13.[Ovechkin A.M. Chronic postoperative pain — the value of the problem and methods of prevention. Russian journal of pain. 2016; 1: 3–13 (In Russ)]
  3. Овечкин А.М. Клиническая фармакология местных анестетиков: классические представления и новые перспективы применения в интенсивной терапии. Регионарная анестезия и лечение острой боли. 2013; 3: 6–15.[Ovechkin A.M. Clinical pharmacology of local anesthetics: classical concepts and new perspectives of applying in intensive therapy. Regionarnaya anesteziya i lechenie ostroy boli. 2013; 3: 6–15. (In Russ)]
  4. Melzalzack R. The MacGill pain questionnaire: major properties and scoring metods. Pain. 1975; 1: 277–299. DOI: 10.1016/0304–3959(75)90044-5
  5. Lamberts M.P., Lugtenberg M., Rovers M.M., et al. Persistent and de novo symptoms after cholecystectomy: a systematic review of cholecystectomy effectiveness. Surg. Endosc. 2013; 27: 709–718. DOI: 10.1007/s00464-012-2516-9
  6. Perkins F.M., Kehlet H. Chronic pain as an outcome of surgery. A review of predictive factors. Anesthesiology. 2000; 93: 1123–1133.
  7. Kehlet H., Jensen T.S., Woolf C.J. Persistent postsurgical pain: Risk factors and prevention. Lancet. 2006; 367: 1618–1625. DOI: 10.1016/S0140–6736(06)68700-X
  8. Bennett G.J. Update on the neurophysiology of pain transmission and modulation: focus on the NMDA-receptor. J. Pain Symptom. Manage. 2000; 19: 2–6. DOI: 10.1016/S0885-3924(99)00120-7
  9. Chizh B.A., Headley P.M. NMDA antagonists and neuropathic pain: multiple drug targets and multiple uses. Curr. Pharm. Des. 2005; 11: 2977–2994. DOI: 10.2174/1381612054865082
  10. Eide P.K. Wind-up and the NMDA receptor complex from a clinical perspective. Eur. J. Pain. 2000; 4: 5–15. DOI: 10.1053/eujp.1999.0154
  11. Parsons C.G. NMDA receptors as targets for drug action in neuropathic pain. Eur. J. Pharmacol. 2001; 429: 71–78. DOI: 10.1016/S0014–2999(01)01307-3
  12. Ji R.R., Xu Z.Z., Gao Y.J. Emerging targets in neuroinflammation-driven chronic pain. Nature reviews Drug discovery. 2014; 13(7): 533–548. DOI: 10.1038/nrd4334
  13. Yardeni I., Beilin B., Mayburd E., et al. The Effect of Perioperative Intravenous Lidocaine on Postoperative Pain and Immune Function. Anesth. Analg. 2009; 109(5): 1464–1469. DOI: 10.1213/ANE.0b013e3181bab1bd
  14. De Oliveira C.M.B., Sakatad R.K., Slullitel A., et al. Issy Efecto de la lidocaina venosa intraoperatoria sobre el dolor e interleucina-6 plasmatica en pacientes sometidas a histerectomia Atenciуn Primaria. 2015; 65(2): 92–98. DOI: 10.1016/j.bjanes.2013.07.018
  15. Сивков О.Г., Устюжанин П.А., Чармадов С.И., Варданян М.А. Опыт безопиоидной анестезии при больших абдоминальных операциях. Медицинская наука и образование Урала. 2018; 4: 104–108.[Sivkov O.G., Ustyuzhanin P.A., Charmadov S.I., Vardanyan M.A. The experience of application of the opioid-free anesthesia during major abdominal surgery. Mediczinskaya nauka i obrazovanie Urala. 2018; 4: 104–108 (In Russ)]
  16. Овечкин А.М., Беккер А.А. Внутривенная инфузия лидокаина как перспективный компонент мультимодальной анальгезии, влияющий на течение раннего послеоперационного периода. Регионарная анестезия и лечение острой боли. 2017; 11(2): 73–83. DOI: 10.18821/1993-6508-2017-11-2-73-83 [Ovechkin A.M., Becker A.A. Intravenous lidocaine infusion as a perspective component of multimodal analgesia, which affects on early postoperative outcome. Regionarnaya anesteziya i lechenie ostroy boli. 2017; 11(2): 73–83. DOI: 10.18821/1993-6508-2017-11-2-73-83. (In Russ)]
  17. Ness T.J. Intravenous lidocaine inhibits visceral nociceptive reflexes and spinal neurons in the rat. Anesthesiology. 2000; 92: 1685–1691.
  18. Groudine S.B., Fisher H.A., Kaufman R.P.Jr., et al. Intravenous lidocaine speeds the return of bowel function, decreases postoperative pain, and shortens hospital stay in patients undergoing radical retropubic prostatectomy. Anesth. Analg. 1998; 86(2): 235–239. DOI: 10.1213/00000539-199802000-00003
  19. Kranke P., Jokinen J., Pace N.L., et al. Continuous intravenous perioperative lidocaine infusion for postoperative pain and recovery. The Cochrane database of systematic reviews. 2015; 7: CD009642. DOI: 10.1002/14651858.CD009642.pub2
  20. Grigoras A., Lee P., Sattar F., Shorten G. Perioperative Intravenous Lidocaine Decreases the Incidence of Persistent Pain After Breast Surgery. Clin. J. Pain. 2012; 28: 567–572. DOI: 10.1097/AJP.0b013e31823b9cc8.

Experience with the use of selective plasma exchange in patients with newly detected secreting multiple myeloma

N.E. Zuderman, N.D. Ushakova, I.B. Lysenko, N.V. Nikolaeva, E.A. Kapuza

Rostov research institute of oncology, Rostov-on-Don

For correspondence: Natalia Е. Zuderman, doctor anesthesiologist-resuscitator of the Block of extracorporeal methods of treatment of anesthesiology and resuscitation department of the Rostov Research Oncology Institute of the Ministry of Health of the Russian Federation, Rostov-on-Don; e-mail:

For citation: Zuderman NE, Ushakova ND, Lysenko IB, Nikolaeva NV, Kapuza EA. Experience with the use of selective plasma exchange in patients with newly detected secreting multiple myeloma. Alexander Saltanov Intensive Care Herald. 2019;2:98–104.

DOI: 10.21320/1818-474X-2019-2-98-104

The prospects of using the selective plasma exchange in the treatment of first identified multiple myeloma (secretory) is substantiated (MM). Twenty-four patients (16 men and 8 women) were examined with stage II−III of the disease. Patients were divided into two groups: the main group (n = 13) with inclusion in therapy selective plasma exchange were included in the treatment and a control group (n = 11) — were treated according to standard protocol. The patients received specific treatment according to the VCD scheme. The concentrations of paraprotein, free light chains Ig (FLC), glomerular filtration rate (GFR), blood toxicity and the functional characteristics of albumin were studied. The studies were conducted before and after the completion of chemotherapy. Additionally, the concentration of paraprotein, FLC and MSM (molecules with average mass) in the blood serum were determined before and 30 min after the end of selective plasma exchange, as well as in the plasma filtrate. The results of the study showed that the inclusion of selective plasma exchange in the treatment ensured the excretion of more than 50 % of the paraprotein and FLC in the blood, a decrease in their concentration after the completion of the procedure: paraprotein 32 %, κ — FLC 43 %, λ — FLC 68 %. There was a greater regression of monoclonal protein levels and FLC production with a marked decrease in the indices of endogenous intoxication and an improvement in the functional properties of the albumin in the main group as compared with the control after completing the chemotherapy course. In the group of patients a more best to the therapy was obtained: a good response — in 69.2 % of the patients (in the control group — in 45.5 %); a negative response — in 30.8 % of cases against 54.5 % in the control group. The obtained results suggested that including selective plasma exchange in the specific complex therapy of patients with first identified multiple myeloma allows to reduce the volume of paraprotein, increase the degree and rate of reduction of LC, without affecting the toxicity of the therapy, which contributes to the strengthening of hematological and renal response to ongoing treatment.

Keywords: First identified multiple myeloma, selective plasma exchange

Received: 15.02.2019


  1. Рыжко В.В., Бирюкова Л.С., Чавынчак Р.Б., Клодзинский А.А. Почечная недостаточность при множественной миеломе. Обзор литературы и собственные данные. Клиническая онкогематология. 2009; 2(4): 316–325. [Ryzhko V.V., Biryukova L.S., Chavynchak R.B., Klodzinskiy A.A. Efficacy of extracorporeal methods in the elimination of light chains in patients with multiple myeloma on programmed hemodialysis. Klinicheskaya onkogematologiya. 2009; 2(4): 316–325. (In Russ)]
  2. San-Miguel J.F., Mateos M.-V. How to treat a newly diagnosed young patient with multiple myeloma. Hematology (American Society of Hematology Education Program Book, New Orleans, Louisiana, December 508, 2009); 2009: 555–565.
  3. Рехтина И.Г., Менделеева Л.П., Варламова Е.Ю., Бирюкова Л.С. Сравнение эффективности бортезомибсодержащих программ в достижении раннего гематологического и почечного ответа у больных миеломной нефропатией с диализзависимой почечной недостаточностью. Гематология и трансфузиология. 2015; 60(4): 4–7. [Rekhtina I.G., Mendeleeva L.P., Varlamova E.Yu., Biryukova L.S. Comparison of the effectiveness of bortezomibsoderzhaschih programs in achieving early hematological and renal response in patients with myeloma nephropathy with dialysis-dependent renal failure. Gematologiya i transfuziologiya. 2015; 60(4): 4–7. (In Russ)]
  4. Dimopoulos M.A., Terpos E., Chanan-Khan A., et al. Renal impairment in patients with multiple myeloma: a consensus statement on behalf of the international myeloma working group. J. Clin. Oncology. 2010; 28(33): 4976–4984.
  5. Бессмельцев С.С., Абдулкадыров К.М., Замотина Т.Б. Лечебный плазмаферез в лечении больных с множественной миеломой. Эфферентная терапия. 2001; 3: 34–43. [Bessmelʼtsev  S.S., Abdulkadyrov K.M., Zamotina T.B. Therapeutic plasmapheresis in the treatment of patients with multiple myeloma. Efferentnaya terapiya. 2001; 3: 34–43. (In Russ)]
  6. Диагностика и лечение множественной миеломы Рекомендации Британского форума по множественной миеломе и Скандинавской исследовательской группы по множественной миеломе. 2005. [Diagnosis and treatment of multiple myeloma Recommendations of the British Forum on Multiple Myeloma and the Scandinavian Multiple Myeloma Research Group. 2005. (In Russ)]
  7. Рехтина И.Г., Марьина С.А., Тангиева Л.М. и др. Эффективность экстракорпоральных методов в элиминации легких цепей у больных множественной миеломой на программном гемодиализе. Гематология и трансфузиология. 2013; 58(2). [Rekhtina I.G., Marʼina S.A., Tangieva L.M., et al. Efficacy of extracorporeal methods in the elimination of light chains in patients with multiple myeloma on programmed hemodialysis. Gematologiya i transfuziologiya. 2013; 58(2). (In Russ)]