日本集中治療医学会・日本救急医学会 合同作成 「日本版敗血症診療ガイドライン2016」 The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG2016)の公開を2016年12月27日（火）より行います。正式版は，2017年2月に両学会機関誌のガイドライン増刊号として同時出版される予定です。正式版では軽微な修正が入るなどにより，先行公開版と異なる可能性がありますので御留意下さい。
Paul E Marik MD
Crit Care. 2011; 15(3): 158.
PMCID: PMC3218964
Glucocorticoids in sepsis: dissecting facts from fiction
An intact hypothalamic-pituitary-adrenal (HPA) axis with effective intracellular glucocorticoid anti-inflammatory activity is essential for host survival following exposure to an infectious agent. Glucocorticoids play a major role in regulating the activity of nuclear factorkappa- B, which has a crucial and generalized role in inducing cytokine gene transcription after exposure to an invading pathogen. Severe sepsis is, however, associated with complex alterations of the HPA axis, which may result in decreased production of cortisol as well as glucocorticoid tissue resistance.
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Inadequate intracellular glucocorticoid activity, referred to as critical illness-related corticosteroid insufficiency, typically results in an exaggerated proinflammatory response [1]. Patients with severe sepsis or septic shock are therefore frequently treated with exogenous glucocorticoids. While there are large geographic variations in the prescription of glucocorticoids for sepsis, up to 50% of intensive care unit patients receive such therapy [2]. Despite over 30 years of investigation and over 20 meta-analyses, the use of glucocorticoids in patients with sepsis remains extremely controversial and recommendations are conflicting.
The most important recent studies are that of Annane and colleagues [3] and the Corticosteroid Therapy of Septic Shock (CORTICUS) study [4]. Both of these studies have important limitations: 24% patients received etomidate in the study by Annane and colleagues, whereas 19% received etomidate in the CORTICUS study. The benefit of steroids in the study by Annane and colleagues may have been restricted largely to those patients who received etomidate [5]. Furthermore, only patients with 'refractory septic shock' were enrolled in the Annane study whereas, as a result of an overwhelming selection bias, only approximately 5% of eligible patients were enrolled in the CORTICUS study [6]. A more recent study found no benefit from a 7-day course of 40 mg of prednisolone in patients hospitalized with community-acquired pneumonia [7].
In the study by Annane and colleagues [3], patients received 50 mg of hydrocortisone intravenously every 6 hours for 7 days, whereas in the CORTICUS study [4], patients received this dose for 5 days, followed by a tapering off over a further 5 days. Recently, two longitudinal studies in patients with severe community-acquired pneumonia found high levels of circulating inflammatory cytokines 3 weeks after clinical resolution of sepsis [8,9]. These data suggest that patients with severe sepsis may have prolonged immune dysregulation (even after clinical recovery) and that a longer course of corticosteroids may be required. The use of a continuous infusion of hydrocortisone has been reported to result in better glycemic control with less variability of blood glucose concentration [10]. This may be clinically relevant as it has been demonstrated that an oscillating blood glucose level is associated with greater oxidative injury than sustained hyperglycemia [11]. Indeed, a number of reports indicate that glucose variability may be an independent predictor of outcome in critically ill patients [12]. A continuous infusion of glucocorticoid may, however, result in greater suppression of the HPA axis. Furthermore, different glucocorticoids differentially affect gene transcription and have differing pharmacodynamic effects. Consequently, the preferred glucocorticoid and the optimal dosing strategy in patients with septic shock remain to be determined.
Evidence-based medicine is defined as the use of the best current scientific evidence in making decisions about the care of individual patients. Owing to the dearth of high-level evidence, it is not possible to make strong evidence-based recommendations on the use of glucocorticoids in patients with sepsis. Therefore, at this juncture, it is useful to summarize what we know, what we think we know, and what we do not know in order to lay the foundation for future scientific exploration; this information is summarized in Table 1.
In summary, the risk/benefit ratio of glucocorticoids should be determined in each patient. A course (7 to 10 days) of low-dose hydrocortisone (200 mg/day) should be considered in vasopressor-dependent patients (dosage of norepinephrine or equivalent of greater than 0.1 μg/kg per minute) within 12 hours of the onset of shock [1]. Steroids should be stopped in patients whose vasopressor dependency has not improved with 2 days of glucocorticoids. While the outcome benefit of low-dose glucocorticoids remains to be determined, such a strategy decreases vasopressor dependency and appears to be safe (no excess mortality, superinfections, or acute myopathy). Infection surveillance is critical in patients treated with corticosteroids, and to prevent the rebound phenomenon, the drug should be weaned slowly. At this time, glucocorticoids appear to have a limited role in patients who have sepsis or severe sepsis and who are at a low risk of dying.
Table 1
Current knowledge concerning glucocorticoids in sepsis
ステロイド療法における今後の展開が，よくまとめられています。
What we know
• Sepsis causes complex alterations of the hypothalamic-pituitary-adrenal axis and glucocorticoid signaling [1].
• Etomidate causes suppression of cortisol synthesis for up to 24 hours [13].
• High random cortisol levels are a marker of disease severity and a poor prognostic marker [14].
• Short-course, high-dose glucocorticoids are not beneficial in the treatment of severe sepsis/septic shock [15-17].
• Treatment of septic shock with moderate-dose glucocorticoids for 7 days significantly reduces vasopressor dependency (adrenocorticotropin responders and non-responders) and intensive care unit length of stay [15-17].
• Glucocorticoids do not increase the risk of superinfections [15-17].
What we think we know
• Glucocorticoids may reduce mortality in subgroups of patients with septic shock [15-17].
• Glucocorticoids appear to be of no benefit in community-acquired pneumonia patients who are at a low risk of dying [7].
• The addition of fludrocortisone does not appear to have additional benefits when treating patients with hydrocortisone [18].
• Treatment with glucocorticoids may reduce the risk of post-traumatic stress disorder [19].
What we do not know
• Which patients with severe sepsis/septic shock should be treated with glucocorticoids?
• Should treatment with glucocorticoids be based on the results of a cosyntropin stimulation test?
• What is the treatment window? Twenty-four hours?
• How does one accurately diagnose adrenal insufficiency and inadequate cellular glucocorticoid activity?
• What is the optimal dosing schedule of glucocorticoids?
• Which glucocorticoid - methylprednisolone or hydrocortisone - should be used?
• Do glucocorticoids cause long-term myopathy?
• Do we need to treat a patient with glucocorticoids if he or she has received etomidate in the previous 24 hours?
References
1. Marik PE. Critical illness related corticoseroid insufficiency. Chest. 2009;135:181–193. doi: 10.1378/chest.08-1149. [PubMed] [Cross Ref]
2. Beale R, Janes JM, Brunkhorst FM, Dobb G, Levy MM, Martin GS, Ramsey G, Silva E, Sprung C. Global utilization of low-dose corticosteroids in severe sepsis and septic shock: a report from the PROGRESS registry. Crit Care. 2010;14:R102. doi: 10.1186/cc8334. [PMC free article] [PubMed] [Cross Ref]
3. Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaut P, Bellissant E. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002;288:862–871. doi: 10.1001/jama.288.7.862. [PubMed] [Cross Ref]
4. Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, Laterre PF, Reinhart K, Cuthbertson BH, Payen D, Briegel J. Hydrocortisone therapy for patients with septic shock. N Engl J Med. 2008;358:111–124. doi: 10.1056/NEJMoa071366. [PubMed] [Cross Ref]
5. Murray H, Marik PE. Etomidate for endotracheal intubation in sepsis: acknowledging the good while accepting the bad. Chest. 2005;127:707–709. doi: 10.1378/chest.127.3.707. [PubMed] [Cross Ref]
6. Marik PE, Pastores SM, Kavanaugh BP. Selection bias negates conclusions from the CORTICUS study? N Engl J Med. 2008;358:2069–2070. [PubMed]
7. Snijders D, Daniels JM, de Graaff CS, van der Werf TS, Boersma WG. Efficacy of corticosteroids in community-acquired pneumonia: a randomized double-blinded clinical trial. Am J Respir Crit Care Med. 2010;181:975–982. doi: 10.1164/rccm.200905-0808OC. [PubMed] [Cross Ref]
8. Kellum JA, Kong L, Fink MP, Weissfeld LA, Yealy DM, Pinsky MR, Fine J, Krichevsky A, Delude RL, Angus DC. Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study. Arch Intern Med. 2007;167:1655–1663. doi: 10.1001/archinte.167.15.1655. [PubMed] [Cross Ref]
9. Lekkou A, Karakantza M, Mouzaki A, Kalfarentzos F, Gogos CA. Cytokine production and monocyte HLA-DR expression as predictors of outcome for patients with community-acquired severe infections. Clin Diagn Lab Immunol. 2004;11:161–167. [PMC free article] [PubMed]
10. Weber-Carstens S, Deja M, Bercker S, Dimroth A, Ahlers O, Kaisers U, Keh D. Impact of bolus application of low-dose hydrocortisone on glycemic control in septic shock patients. Intensive Care Med. 2007;33:730–733. doi: 10.1007/s00134-007-0540-3. [PubMed] [Cross Ref]
11. Ceriello A, Esposito K, Piconi L, Ihnat MA, Thorpe JE, Testa R, Boemi M, Giugliano D. Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes. 2008;57:1349–1354. doi: 10.2337/db08-0063. [PubMed] [Cross Ref]
12. Egi M, Bellomo R, Stachowski E, French CJ, Hart G. Variability of blood glucose concentration and short-term mortality in critically ill patients. Anesthesiology. 2006;105:244–252. doi: 10.1097/00000542-200608000-00006. [PubMed] [Cross Ref]
13. Vinclair M, Broux C, Faure C, Brun J, Gentry C, Jacquot C, Chabre O, Payen JF. Duration of adrenal inhibition following a single dose of etomidate in critically ill patients. Intensive Care Med. 2008;34:714–719. doi: 10.1007/s00134-007-0970-y. [PubMed] [Cross Ref]
14. Annane D, Sebille V, Troche G, Raphael JC, Gajdos P, Bellissant E. A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA. 2000;283:1038–1045. doi: 10.1001/jama.283.8.1038. [PubMed] [Cross Ref]
15. Annane D, Bellissant E, Bollaert PE, Briegel J, Confalonieri M, De Gaudio R, Keh D, Kupfer Y, Oppert M, Meduri GU. Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review. JAMA. 2009;301:2349–2361. doi: 10.1001/jama.2009.813. [PMC free article] [PubMed] [Cross Ref]
16. Moran JL, Graham PL, Rockliff S, Bersten AD. Updating the evidence for the role of corticosteroids in severe sepsis and shock: a Bayesian metaanalytic perspective. Crit Care. 2010;14:R134. doi: 10.1186/cc9182. [PMC free article] [PubMed] [Cross Ref]
17. Sligl WI, Milner DA, Sundarr S, Mphatswe W, Majumdar SR. Safety and efficacy of corticosteroids for the treatment of septic shock: a systematic review and meta-analysis. Clin Infect Dis. 2009;49:93–101. doi: 10.1086/599343. [PubMed] [Cross Ref]
18. COIITSS Study Investigators. Annane D, Cariou A, Maxime V, Azoulay E, D'honneur G, Timsit JF, Cohen Y, Wolf M, Fartoukh M, Adrie C, Santré C, Bollaert PE, 17. Mathonet A, Amathieu R, Tabah A, Clec'h C, Mayaux J, Lejeune J, Chevret S. Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial. JAMA. 2010;303:341–348. [PubMed]
19. Schelling G, Briegel J, Roozendaal B, Stoll C, Rothenhäusler HB, Kapfhammer HP. The effect of stress doses of hydrocortisone during septic shock on posttraumatic stress disorder in survivors. Biol Psychiatry. 2001;50:978–985. doi: 10.1016/S0006-3223(01)01270-7.
Jim Tibballs MD
Dr Jim Tibballs, Deputy Director of Intensive Care at the Royal Children's Hospital in Melbourne, was involved in venom research with Prof. Sutherland for many years. His research interests have included the cardiovascular effects of box jellyfish venom, brown snake procoagulants and most recently the clinical effects of the irukandji syndrome. This research was presented at the 6th World Congress of the International Society on Toxinology in Paris, September 2000. He became an honorary senior associate of the Australian Venom Research Unit in 1997. In 1998, he completed his MD in toxinology, and he also has a masters degree in education. With Professor Struan Sutherland he co-authored the second edition of "Australian Animal Toxins” published in 2001.
小児蘇生に関する文献
1. Basic and advanced paediatric cardiopulmonary resuscitation - Guidelines of the Australian and New Zealand Resuscitation Councils 2010.
Tibballs J, Aickin R, Nuthall G; On behalf of the Australian and New Zealand Resuscitation Councils.
J Paediatr Child Health. 2012 Jul;48(7):551-555.
Guidelines for basic and advanced paediatric cardiopulmonary resuscitation (CPR) have been revised by Australian and New Zealand Resuscitation Councils. Changes encourage CPR out-of-hospital and aim to improve the quality of CPR in-hospital. Features of basic CPR include: omission of abdominal thrusts for foreign body airway obstruction; commencement with chest compression followed by ventilation in a ratio of 30:2 or compression-only CPR if the rescuer is unwilling/unable to give expired-air breathing when the victim is 'unresponsive and not breathing normally'. Use of automated external defibrillators is encouraged. Features of advanced CPR include: prevention of cardiac arrest by rapid response systems; restriction of pulse palpation to 10 s to diagnosis cardiac arrest; affirmation of 15:2 compression-ventilation ratio for children and for infants other than newly born; initial bag-mask ventilation before tracheal intubation; a single direct current shock of 4 J/kg for ventricular fibrillation (VF) and pulseless ventricular tachycardia followed by immediate resumption of CPR for 2 min without analysis of cardiac rhythm and avoidance of unnecessary interruption of continuous external cardiac compressions. Monitoring of exhaled carbon dioxide is recommended to detect non-tracheal intubation, assess quality of CPR, and to help match ventilation to reduced cardiac output. The intraosseous route is recommended if immediate intravenous access is impossible. Amiodarone is strongly favoured over lignocaine for refractory VF and adrenaline over atropine for severe bradycardia, asystole and pulseless electrical activity. Family presence at resuscitation is encouraged. Therapeutic hypothermia is acceptable after resuscitation to improve neurological outcome. Extracorporeal circulatory support for in-hospital cardiac arrest may be used in equipped centres.
2. Pediatric basic and advanced life support: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations.
Kleinman ME, de Caen AR, Chameides L, Atkins DL, Berg RA, Berg MD, Bhanji F, Biarent D, Bingham R, Coovadia AH, Hazinski MF, Hickey RW, Nadkarni VM, Reis AG, Rodriguez-Nunez A, Tibballs J, Zaritsky AL, Zideman D; Pediatric Basic and Advanced Life Support Chapter Collaborators.
Pediatrics. 2010 Nov;126(5):e1261-318.
3. Part 10: Pediatric basic and advanced life support: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.
Kleinman ME, de Caen AR, Chameides L, Atkins DL, Berg RA, Berg MD, Bhanji F, Biarent D, Bingham R, Coovadia AH, Hazinski MF, Hickey RW, Nadkarni VM, Reis AG, Rodriguez-Nunez A, Tibballs J, Zaritsky AL, Zideman D; Pediatric Basic and Advanced Life Support Chapter Collaborators.
Circulation. 2010 Oct 19;122(16 Suppl 2):S466-515.
4. External and internal biphasic direct current shock doses for pediatric ventricular fibrillation and pulseless ventricular tachycardia.
Tibballs J, Carter B, Kiraly NJ, Ragg P, Clifford M.
Pediatr Crit Care Med. 2011 Jan;12(1):14-20.
OBJECTIVE:
To determine energy dose and number of biphasic direct current shocks for pediatric ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT).
DESIGN:
Observation of preshock and postshock rhythms, energy doses, and number of shocks.
SETTING:
Pediatric hospital.
PATIENTS:
Shockable ventricular dysrhythmias.
INTERVENTIONS:
None.
MEASUREMENTS AND MAIN RESULTS:
Forty-eight patients with VF or pulseless VT received external shock at 1.7 ± 0.8 (mean ± SD) J/kg. Return of spontaneous circulation (ROSC) occurred in 23 (48%) patients with 2.0 ± 1.0 J/kg, but 25 (52%) patients remained in VF after 1.5 ± 0.7 J/kg (p = .05). In 24 non-responding patients, additional 1-8 shocks (final dose, 2.8 ± 1.2 J/kg) achieved ROSC in 14 (58%) with 2.6 ± 1.1 J/kg but not in 10 (42%) with 3.2 ± 1.2 J/kg (not significant). Overall, 37 (77%) patients achieved ROSC with 2.2 ± 1.1 J/kg (range, 0.5-5.0 J/kg). Eight patients without ROSC recovered with cardiopulmonary bypass and internal direct current shock. At 13 subsequent episodes of VF or VT among eight patients, five achieved ROSC and survived. In combined first and subsequent resuscitative episodes, doses in the range of 2.5 to < 3 J/kg achieved most cases of ROSC. Survival for > 1 yr was seen in 28 (78%) of 36 patients with VF and seven (58%) of 11 patients with VT, with 35 (73%) overall. Lack of ROSC was associated with multiple shocks (p = .003). Repeated shocks with adhesive pads had significantly less impedance (p < .001). Pads in an anteroposterior position achieved highest ROSC rate. Internal shock for another 48 patients with VF or VT achieved ROSC in 28 (58%) patients with 0.7 ± 0.4 J/kg but not in 20 patients with 0.4 ± 0.3 J/kg (p = .01). Nineteen of the nonresponders who received additional internal 1-9 shocks at 0.6 ± 0.5 J/kg and one patient given extracorporeal membrane oxygenation all recovered, yielding 100% ROSC, but 1-yr survival tallied 43 (90%) patients.
CONCLUSIONS:
The initial biphasic direct current external shock dose of 2 J/kg for VF or pulseless VT is inadequate. Appropriate doses for initial and subsequent shocks seem to be in the range of 3-5 J/kg. Multiple shocks do not favor ROSC. The dose for internal shock is 0.6-0.7 J/kg.
＜追加文献＞
1. Gutgesell HP, Tacker WA, Geddes LA, et al: Energy dose for ventricular defibrillation of children. Pediatrics 1976; 58:898-901
2. Tibballs J, Kinney S: A prospective study of outcome of in-patient paediatric cardiopulmonary arrest. Resuscitation 2006; 71:310-318
3. Rodriguez-Nunez A, Lopez-Herce J, Garcia C, et al: Pediatric defibrillation after cardiac arrest: Initial response and outcome. Crit Care 2006; 10:R113
4. Rossano JW, Quan L, Kenney MA, et al: Energy doses for treatment of out-of-hospital pediatric ventricular fibrillation. Resuscitation 2006; 70:80-89
5. Berg MD, Samson RA, Meyer RJ, et al: Pediatric defibrillation doses often fail to terminate prolonged out-of-hospital ventricular fibrillation in children. Resuscitation 2005; 67:63-67
6. Gurnett CA, Atkins DL: Successful use of a biphasic waveform automated external defibrillator in a high-risk child. Am J Cardiol 2000; 86:1051-1053
7. Atkins DL, Jorgenson DB: Attenuated pediatric electrode pads for automated external defibrillator use in children. Resuscitation 2005; 66:31-37
8. Konig B, Benger J, Goldsworthy L: Automatic external defibrillation in a 6 year old. Arch Dis Child 2005; 90:310-311
9. Divekar A, Soni R: Successful parental use of an automated external defibrillator for an infant with long-QT syndrome. Pediatrics 2006; 118:e526-e529
10. Berg RA, Chapman FW, Berg MD, et al: Attenuated adult biphasic shocks compared with weight-based monophasic shocks in a swine model of prolonged pediatric ventricular fibrillation. Resuscitation 2004; 61:189-197
11. Berg RA, Samson RA, Berg MD, et al: Better outcome after pediatric defibrillation dosage than adult dosage in a swine model of pediatric ventricular fibrillation. J Am Coll Cardiol 2005; 45:786-789
12. Clark CB, Zhang Y, Davies LR, et al: Pediatric transthoracic defibrillation: Biphasic versus monophasic waveforms in an experimental model. Resuscitation 2001; 51:159-163
13. Killingsworth CR, Melnick SB, Chapman FW, et al: Defibrillation threshold and cardiac responses using an external biphasic defibrillator with pediatric and adult adhesive patches in pediatric-sized piglets. Resuscitation 2002; 55:177-185
14. Jacobs IG, Tibballs J, Morley PT, et al: Energy levels for biphasic defibrillation. Med J Aust 2003; 179:451
15. American Heart Association: Part 12: Pediatric Advanced Life Support. Circulation 2005; 112:IV-167-IV-187
16. Australian Resuscitation Council: Resuscitation guideline 12.5. Available at http://www.resus.org. Accessed July 15, 2009
17. Biarent D, Bingham R, Richmond S, et al: European Resuscitation Council Guidelines for resuscitation 2005 Section 6. Paediatric life support. Resuscitation 2005; 67S1:S97-S133
18. Tibballs J, Kinney S: Reduction of hospital mortality and of preventable cardiac arrest and death on introduction of a pediatric medical emergency team. Pediatr Crit Care Med 2009; 10:306-312
19. van Alem AP, Chapman FW, Lank P, et al: A prospective, randomised and blinded comparison of first shock success of monophasic and biphasic waveforms in out-of-hospital cardiac arrest. Resuscitation 2003; 58:17-24
20. Eftestol T, Sunde K, Steen PA: Effects of interrupting precordial compressions on the calculated probability of defibrillation success during out-of-hospital cardiac arrest. Circulation 2002; 105:2270-2273
21. Edelson D, Abella B, Kramer-Johansen J, et al: Effects of compression depth and pre-shock pauses predict defibrillation failure during cardiac arrest. Resuscitation 2006; 71:137-145
22. Valenzuela TD, Roe DJ, Nichol G, et al: Outcomes of rapid defibrillation by security officers after cardiac arrest in casinos. N Engl J Med 2000; 343:1206-1209
23. Chan PS, Krumholz HM, Nichol G, et al: Delayed time to defibrillation after in-hospital cardiac arrest. N Engl J Med 2008; 358:9-17
25. Samson RA, Nadkarni VM, Meaney PA, et al: Outcomes of in-hospital ventricular fibrillation in children. N Eng J Med 2006; 354:2328-2339
26. Samson R, Atkins DL, Kerber RE: Optimal size of self-adhesive preapplied electrode pads in pediatric defibrillation. Am J Cardiol 1995; 75:544-545
27. Nadkarni VM, Larkin GL, Peberdy MA, et al: First documented rhythm and clinical outcomes from in-hospital cardiac arrest among children and adults. JAMA 2006; 295:50-57
28. Perkins GD, Roberts C, Gao F: Delays in defibrillation: influence of different monitoring techniques. Br J Anaesth 2002; 89:405-408
29. Perkins GD, Davies RP, Soar J, et al: The impact of manual defibrillation technique on no-flow time during simulated cardiopulmonary resuscitation. Resuscitation 2007; 73:109-114
30. Garcia LA, Kerber RE: Transthoracic defibrillation: Does electrode adhesive pad position alter transthoracic impedance? Resuscitation 1998; 37:139-143
31. Deakin C, Bennetts S, Petley G, et al: What is the optimal paddle force for paediatric defibrillation. Resuscitation 2002; 55:59
32. Bennetts SH, Deakin CD, Petley GW, Clewlow F: Is optimal paddle force applied during paediatric external defibrillation? Resuscitation 2004; 60:29-32
Predictors of prolonged vasopressin infusion for the treatment of septic shock
Journal of Critical Care (2012) 27, 318.e7–318.e12
Heather A. Personett PharmD, Joanna L. Stollings PharmD,
Stephen S. Cha MS, Lance J. Oyen PharmD, FCCM, FCCP
Department of Pharmacy Services at Mayo Clinic, Rochester, Minnesota
Department of Biostatistics and Informatics at Mayo Clinic, Rochester, Minnesota
PURPOSE:Prolonged catecholamine use has been linked with poor clinical outcomes, including higher mortality. The objective was to identify characteristics that may be predictive of prolonged arginine vasopressin (AVP) use for 7 days or more in patients with septic shock.
MATERIALS AND METHODS:This was a retrospective nested cohort analysis of adult patients receiving AVP as initial hemodynamic support for septic shock, either alone or in combination with norepinephrine, between 2008 and 2010.
RESULTS:Univariate factors predictive of patients requiring extended AVP support were peripheral vascular disease (PVD) (48% vs 18%, P = .001), congestive heart failure (30% vs 12%, P = .024), and acute kidney injury (AKI) (83% vs 49%, P = .003). Patients requiring extended AVP support more frequently experienced a new intensive care unit (ICU) arrhythmia, typically atrial fibrillation (39% vs 7%, P < .001), and had higher 28-day mortality (74% vs 20%, P < .001). Multivariate analysis revealed that the strongest independent predictors of prolonged AVP dependence were new ICU arrhythmia (odds ratio [OR], 5.3; 95% confidence interval [CI], 1.6-17.8), PVD (OR, 4.3; 95% CI, 1.4-13.1), and AKI (OR, 3.9; 95% CI, 1.1-14.5).
CONCLUSIONS:Patients with preexisting PVD and AKI and those experiencing a new ICU arrhythmia on AVP may be more likely to remain on AVP for 7 or more days.
＜コメント＞ バソプレシンを7日以上に渡って長期投与することは僕はしません。そうならないように，どのように敗血症や全身性炎症の管理をするかが大切と思います。血管内皮細胞障害を合併した状態では，細動脈血管平滑筋領域のV1受容体の反応が血管収縮，血管攣縮として局所的に強く出可能性があり，つまり血管収縮作用が高まるために，バゾプレシンは使用しません。また，既往歴としてPSSなどのレイノー症状を伴う患者さんやコントロールの悪いDM患者さん，つまり，既に血管内皮細胞障害を併発していることが疑われる場合，敗血症性ショックはwarm shockとはなりにくく，はじめからcold shockとして出現するわけではなく，バソプレシンの併用をお勧めしていません。今回は，原点回帰 ROCK ライブの広告も付けてみました。福井が放射能で死の町とならないように，常識的に震災や津波の地理状況を判断し，「脱原発」とすることが望ましいでしょう。予測できる誤りをしないようすすることは，敗血症管理と同様です。 松田直之
子供の救命にはエビデンスを超えて肺酸素化が維持できない場合にECMOをよく使うが，その際に脳機能障害を残さないようにエビデンスを構築していく必要がある。このような脳機能障害の血清マーカーとしてS-100B蛋白はよく知られているが，glial fibrillary acid protein (GFAP)も良いマーカーではないかと注目されている。
Cardiovasc Hematol Agents Med Chem. 2009 Apr;7(2):108-26.
Circulating biochemical markers of brain damage in infants complicated by ischemia reperfusion injury.
Gazzolo D, Abella R, Marinoni E, Di Iorio R, Li Volti G, Galvano F, Pongiglione G, Frigiola A, Bertino E, Florio P.
Hypoxia-ischemia constitutes a risk in infants by altering cerebral blood flow regulatory mechanisms and causing loss of cerebral vascular auto-regulation. Hypotension, cerebral ischemia, and reperfusion are the main events involved in vascular auto-regulation leading to cell death and tissue damage. Reperfusion could be critical since organ damage, particularly of the brain, may be amplified during this period. An exaggerated activation of vasoactive agents of calcium mediated effects could be responsible for reperfusion injury, which, in turns, leads to cerebral hemorrhage and damage. These dramatic phenomena represent a common repertoire in infants complicated by perinatal acute or chronic hypoxia or cardiovascular disorders treated by risky procedures such as open heart surgery and cardiopulmonary by-pass (CPB). To date, despite accurate perinatal and intra-operative monitoring, the post-insult period is crucial, since clinical symptoms and monitoring parameters may be of no avail and therapeutic window for pharmacological intervention (6-12 hours) may be limited, at a time when brain damage is already occurring. Therefore, the measurement of circulating biochemical markers of brain damage, such as vasoactive agents and nervous tissue peptides is eagerly awaited in clinical practice to detect high risk infants. The present review is aimed at investigating the role as circulating biochemical markers such as adrenomedullin, a vasoactive peptide; S100B, a calcium binding protein, activin A, a glycoprotein; neuronal specific enolase (NSE), a dimeric isoenzyme; glial fibrillary acid protein (GFAP), a astroglial protein, in the cascade of events leading to ischemia reperfusion injury in infants complicated by perinatal asphyxia or cardiovascular disorders requiring risky therapeutic strategies such as CPB and/or extracorporeal membrane oxygenation.
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