今日の臨床サポート

ショック(小児科)

著者: 櫻井淑男 埼玉医科大学総合医療センター 小児救命救急センター

監修: 五十嵐隆 国立成育医療研究センター

著者校正/監修レビュー済:2022/06/23
患者向け説明資料

概要・推奨   

  1. 敗血症性ショックの輸液は、身体所見やエコーなどで再評価しながら細胞外液20mL/kgのボーラスを繰り返し投与することが推奨される(推奨度2)
  1. 敗血症性ショックにおいてカテコールアミン治療に抵抗性の場合は、ステロイドを考慮する(推奨度2)
  1. 敗血症の管理時にScvO2が推奨される(推奨度2)
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
櫻井淑男 : 特に申告事項無し[2022年]
監修:五十嵐隆 : 特に申告事項無し[2022年]

改訂のポイント:
  1. 定期レビューを行った(変更なし)。

病態・疫学・診察

疾患情報(疫学・病態)  
ポイント:
  1. ショックとは、末梢組織の酸素と栄養の需要が供給を上回った状態のことである。
  1. ショックの重症度は、代償性ショックと低血圧性ショックの2つに分けられる。
  1. 原因分類として循環血液量減少性ショック、血液分布異常性ショック、心原性ショック、閉塞性ショックの4つに分類される。
  1. 実際の診療では、まず重症度の分類を行い、次に原因分類に進んで治療に結びつけることが大切である。
  1. 小児は予備力が不十分で、早期の治療が良好な予後に結びつくので、ショックを疑う徴候があれば、すぐに検査や治療に入ることが重要である。
 
小児と成人のショックの相違:
  1. 小児は成人と比較して予備力が十分ではない。したがって、代償性ショックの段階を見落として介入せずに低血圧ショックまで持ち込むと重度の後遺症を残したり、致死的な状態となることがある。よって代償性ショックの段階で診断し、介入することがきわめて重要となる。代償性ショックでは、血圧は正常範囲なので血圧のみをショックの診断に用いてはいけない。心拍数や毛細血管再充満時間、その他の身体所見などから総合的に判断することが必要である。
問診・診察のポイント  
  1. 小児の循環障害は成人のように胸痛などの特有な症状で発症することはまれで、意識低下、多呼吸、消化器症状(嘔吐、腹痛、下痢など)のような一般的な症状を示すことが多いので注意が必要である。

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文献 

Allan R de Caen, Ian K Maconochie, Richard Aickin, Dianne L Atkins, Dominique Biarent, Anne-Marie Guerguerian, Monica E Kleinman, David A Kloeck, Peter A Meaney, Vinay M Nadkarni, Kee-Chong Ng, Gabrielle Nuthall, Amelia G Reis, Naoki Shimizu, James Tibballs, Remigio Veliz Pintos, Pediatric Basic Life Support Pediatric Advanced Life Support Chapter Collaborators
Part 6: Pediatric Basic Life Support and Pediatric Advanced Life Support: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations (Reprint).
Pediatrics. 2015 Nov;136 Suppl 2:S88-119. doi: 10.1542/peds.2015-3373C. Epub 2015 Oct 14.
Abstract/Text
PMID 26471382
Timothy M Hoffman, Gil Wernovsky, Andrew M Atz, Thomas J Kulik, David P Nelson, Anthony C Chang, James M Bailey, Akbar Akbary, John F Kocsis, Raymond Kaczmarek, Thomas L Spray, David L Wessel
Efficacy and safety of milrinone in preventing low cardiac output syndrome in infants and children after corrective surgery for congenital heart disease.
Circulation. 2003 Feb 25;107(7):996-1002.
Abstract/Text BACKGROUND: Low cardiac output syndrome (LCOS), affecting up to 25% of neonates and young children after cardiac surgery, contributes to postoperative morbidity and mortality. This study evaluated the efficacy and safety of prophylactic milrinone in pediatric patients at high risk for developing LCOS.
METHODS AND RESULTS: The study was a double-blind, placebo-controlled trial with 3 parallel groups (low dose, 25- microg/kg bolus over 60 minutes followed by a 0.25- microg/kg per min infusion for 35 hours; high dose, 75- microg/kg bolus followed by a 0.75- microg/kg per min infusion for 35 hours; or placebo). The composite end point of death or the development of LCOS was evaluated at 36 hours and up to 30 days after randomization. Among 238 treated patients, 25.9%, 17.5%, and 11.7% in the placebo, low-dose milrinone, and high-dose milrinone groups, respectively, developed LCOS in the first 36 hours after surgery. High-dose milrinone significantly reduced the risk the development of LCOS compared with placebo, with a relative risk reduction of 55% (P=0.023) in 238 treated patients and 64% (P=0.007) in 227 patients without major protocol violations. There were 2 deaths, both after infusion of study drug. The use of high-dose milrinone reduced the risk of the LCOS through the final visit by 48% (P=0.049).
CONCLUSIONS: The use of high-dose milrinone after pediatric congenital heart surgery reduces the risk of LCOS.

PMID 12600913
Satish K Rajagopal, Christopher S Almond, Peter C Laussen, Peter T Rycus, David Wypij, Ravi R Thiagarajan
Extracorporeal membrane oxygenation for the support of infants, children, and young adults with acute myocarditis: a review of the Extracorporeal Life Support Organization registry.
Crit Care Med. 2010 Feb;38(2):382-7. doi: 10.1097/CCM.0b013e3181bc8293.
Abstract/Text OBJECTIVE: To describe survival outcomes for pediatric patients supported with extracorporeal membrane oxygenation for severe myocarditis and identify risk factors for in-hospital mortality.
DESIGN: Retrospective review of Extracorporeal Life Support Organization registry database.
SETTING: Data reported to Extracorporeal Life Support Organization from 116 extracorporeal membrane oxygenation centers.
PATIENTS: Patients < or = 18 yrs of age supported with extracorporeal membrane oxygenation for myocarditis during 1995 to 2006.
INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: Of 19,348 reported pediatric extracorporeal membrane oxygenation uses from 1995 to 2006, 260 runs were for 255 patients with a diagnosis of myocarditis (1.3%). Survival to hospital discharge was 61%. Seven patients (3%) underwent heart transplantation and six patients survived to discharge. Of 100 patients not surviving to hospital discharge, extracorporeal membrane oxygenation support was withdrawn in 70 (70%) with multiple organ failure as the indication in 58 (83%) patients. In a multivariable model, female gender (adjusted odds ratio, 2.3, 95% confidence interval, 1.3-4.2), arrhythmia on extracorporeal membrane oxygenation (adjusted odds ratio, 2.7, 95% confidence interval, 1.5-5.1), and renal failure requiring dialysis (adjusted odds ratio, 5.1, 95% confidence interval, 2.3-11.4) were associated with increased odds of in-hospital mortality.
CONCLUSION: Extracorporeal membrane oxygenation is a valuable tool to rescue children with severe cardiorespiratory compromise related to myocarditis. Female gender, arrhythmia on extracorporeal membrane oxygenation, and need for dialysis during extracorporeal membrane oxygenation were associated with increased mortality.

PMID 19789437
Paul Dorian, Dan Cass, Brian Schwartz, Richard Cooper, Robert Gelaznikas, Aiala Barr
Amiodarone as compared with lidocaine for shock-resistant ventricular fibrillation.
N Engl J Med. 2002 Mar 21;346(12):884-90. doi: 10.1056/NEJMoa013029.
Abstract/Text BACKGROUND: Lidocaine has been the initial antiarrhythmic drug treatment recommended for patients with ventricular fibrillation that is resistant to conversion by defibrillator shocks. We performed a randomized trial comparing intravenous lidocaine with intravenous amiodarone as an adjunct to defibrillation in victims of out-of-hospital cardiac arrest.
METHODS: Patients were enrolled if they had out-of-hospital ventricular fibrillation resistant to three shocks, intravenous epinephrine, and a further shock; or if they had recurrent ventricular fibrillation after initially successful defibrillation. They were randomly assigned in a double-blind manner to receive intravenous amiodarone plus lidocaine placebo or intravenous lidocaine plus amiodarone placebo. The primary end point was the proportion of patients who survived to be admitted to the hospital.
RESULTS: In total, 347 patients (mean [+/-SD] age, 67+/-14 years) were enrolled. The mean interval between the time at which paramedics were dispatched to the scene of the cardiac arrest and the time of their arrival was 7+/-3 minutes, and the mean interval from dispatch to drug administration was 25+/-8 minutes. After treatment with amiodarone, 22.8 percent of 180 patients survived to hospital admission, as compared with 12.0 percent of 167 patients treated with lidocaine (P=0.009; odds ratio, 2.17; 95 percent confidence interval, 1.21 to 3.83). Among patients for whom the time from dispatch to the administration of the drug was equal to or less than the median time (24 minutes), 27.7 percent of those given amiodarone and 15.3 percent of those given lidocaine survived to hospital admission (P=0.05).
CONCLUSIONS: As compared with lidocaine, amiodarone leads to substantially higher rates of survival to hospital admission in patients with shock-resistant out-of-hospital ventricular fibrillation.

PMID 11907287
Santiago O Valdes, Aaron J Donoghue, Derek B Hoyme, Rachel Hammond, Marc D Berg, Robert A Berg, Ricardo A Samson, American Heart Association Get With The Guidelines-Resuscitation Investigators
Outcomes associated with amiodarone and lidocaine in the treatment of in-hospital pediatric cardiac arrest with pulseless ventricular tachycardia or ventricular fibrillation.
Resuscitation. 2014 Mar;85(3):381-6. doi: 10.1016/j.resuscitation.2013.12.008. Epub 2013 Dec 19.
Abstract/Text AIM: To determine the association between amiodarone and lidocaine and outcomes in children with cardiac arrest with pulseless ventricular tachycardia (pVT) and ventricular fibrillation (VF).
BACKGROUND: Current AHA guidelines for CPR and emergency cardiovascular care recommend amiodarone for cardiac arrest in children associated with shock refractory pVT/VF, based on a single pediatric study and extrapolation from adult data.
METHODS: Retrospective cohort study from the Get With the Guidelines-Resuscitation database for in-patient cardiac arrest. Patients<18 years old with pVT/VF cardiac arrest were included. Patients receiving amiodarone or lidocaine prior to arrest or whose initial arrest rhythm was unknown were excluded. Univariate analysis was performed to assess the association between patient and event factors and clinical outcomes. Multivariate analysis was performed to address independent association between lidocaine and amiodarone use and outcomes.
RESULTS: Of 889 patients, 171 (19%) received amiodarone, 295 (33%) received lidocaine, and 82 (10%) received both. Return of spontaneous circulation (ROSC) occurred in 484/889 (54%), 24-h survival in 342/874 (39%), and survival to hospital discharge in 194/889 (22%). Lidocaine was associated with improved ROSC (adjusted OR 2.02, 95% CI 1.36-3), and 24-h survival (adjusted OR 1.66, 95% CI 1.11-2.49), but not hospital discharge. Amiodarone use was not associated with ROSC, 24h survival, or survival to discharge.
CONCLUSIONS: For children with in-hospital pVT/VF, lidocaine use was independently associated with improved ROSC and 24-h survival. Amiodarone use was not associated with superior rates of ROSC, survival at 24h. Neither drug was associated with survival to hospital discharge.

Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
PMID 24361455
Justine Rouette, Helen Trottier, Thierry Ducruet, Mona Beaunoyer, Jacques Lacroix, Marisa Tucci, Canadian Critical Care Trials Group, PALISI Network
Red blood cell transfusion threshold in postsurgical pediatric intensive care patients: a randomized clinical trial.
Ann Surg. 2010 Mar;251(3):421-7. doi: 10.1097/SLA.0b013e3181c5dc2e.
Abstract/Text BACKGROUND: The optimal transfusion threshold after surgery in children is unknown. We analyzed the general surgery subgroup of the TRIPICU (Transfusion Requirements in Pediatric Intensive Care Units) study to determine the impact of a restrictive versus a liberal transfusion strategy on new or progressive multiple organ dysfunction syndrome (MODS).
METHODS: The TRIPICU study, a prospective randomized controlled trial conducted in 17 centers, enrolled a total of 648 critically ill children with a hemoglobin equal to or below 9.5 g/dL within 7 days of pediatric intensive care unit (PICU) admission to receive prestorage leukocyte-reduced red-cell transfusion if their hemoglobin dropped below either 7.0 g/dL (restrictive) or 9.5 g/dL (liberal). A subgroup of 124 postoperative patients (60 randomized to restrictive and 64 to the liberal group) were analyzed. This study was registered at http://www.controlled-trials.com and carries the following ID ISRCTN37246456.
RESULTS: Participants in the restrictive and liberal groups were similar at randomization in age (restrictive vs. liberal: 53.5 +/- 51.8 vs. 73.7 +/- 61.8 months), severity of illness (pediatric risk of mortality [PRISM] score: 3.5 +/- 4.0 vs. 4.4 +/- 4.0), MODS (35% vs. 29%), need for mechanical ventilation (77% vs. 74%), and hemoglobin level (7.7 +/- 1.1 vs. 7.9 +/- 1.0 g/dL). The mean hemoglobin level remained 2.3 g/dL lower in the restrictive group after randomization. No significant differences were found for new or progressive MODS (8% vs. 9%; P = 0.83) or for 28-day mortality (2% vs. 2%; P = 0.96) in the restrictive versus liberal group. However, there was a statistically significant difference between groups for PICU length of stay (7.7 +/- 6.6 days for the restrictive group vs. 11.6 +/- 10.2 days for the liberal group; P = 0.03).
CONCLUSIONS: In this subgroup analysis of pediatric general surgery patients, we found no conclusive evidence that a restrictive red-cell transfusion strategy, as compared with a liberal one, increased the rate of new or progressive MODS or mortality.

PMID 20118780
Ariane Willems, Karen Harrington, Jacques Lacroix, Dominique Biarent, Ari R Joffe, David Wensley, Thierry Ducruet, Paul C Hébert, Marisa Tucci, TRIPICU investigators, Canadian Critical Care Trials Group, Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
Comparison of two red-cell transfusion strategies after pediatric cardiac surgery: a subgroup analysis.
Crit Care Med. 2010 Feb;38(2):649-56. doi: 10.1097/CCM.0b013e3181bc816c.
Abstract/Text OBJECTIVE: To determine the impact of a restrictive vs. a liberal transfusion strategy on new or progressive multiple organ dysfunction syndrome in children post cardiac surgery. The optimal transfusion threshold after cardiac surgery in children is unknown.
DESIGN: Randomized, controlled trial.
SETTING: Tertiary pediatric intensive care units.
PATIENTS: Participants are a subgroup of pediatric patients post cardiac surgery from the TRIPICU (Transfusion Requirements in Pediatric Intensive Care Units) study. Exclusion criteria specific to the cardiac surgery subgroup included: age <28 days and patients remaining cyanotic.
INTERVENTION: Critically ill children with a hemoglobin < or = 95 g/L within 7 days of pediatric intensive care unit admission were randomized to receive prestorage leukocyte-reduced red-cell transfusion if their hemoglobin dropped either <70 g/L (restrictive) or 95 g/L (liberal).
MEASUREMENTS AND MAIN RESULTS: Postoperative cardiac patients (n = 125) from seven centers were enrolled. The restrictive (n = 63) and liberal (n = 62) groups were similar at baseline in age (mean +/- standard deviation = 31.4 +/- 38.1 mos vs. 26.4 +/- 39.1 mos), surgical procedure, severity of illness (Pediatric Risk of Mortality score = 3.4 +/- 3.2 vs. 3.2 +/- 3.2), multiple organ dysfunction syndrome (46% vs. 44%), mechanical ventilation (62% vs. 60%), and hemoglobin (83 vs. 80 g/L). Mean hemoglobin remained 21 g/L lower in the restrictive group after randomization. No significant difference was found in new or progressive multiple organ dysfunction syndrome (primary outcome) in the restrictive group vs. liberal group (12.7% vs. 6.5%; p = .36), pediatric intensive care unit length of stay (7.0 +/- 5.0 days vs. 7.4 +/- 6.4 days) or 28-day mortality (3.2% vs. 3.2%).
CONCLUSION: In this subgroup analysis of cardiac surgery patients, a restrictive red-cell transfusion strategy, as compared with a liberal one, was not associated with any significant difference in new or progressive multiple organ dysfunction syndrome, but this evidence is not definitive.

PMID 19789443
Jill M Cholette, Jeffrey S Rubenstein, George M Alfieris, Karen S Powers, Michael Eaton, Norma B Lerner
Children with single-ventricle physiology do not benefit from higher hemoglobin levels post cavopulmonary connection: results of a prospective, randomized, controlled trial of a restrictive versus liberal red-cell transfusion strategy.
Pediatr Crit Care Med. 2011 Jan;12(1):39-45. doi: 10.1097/PCC.0b013e3181e329db.
Abstract/Text OBJECTIVE: To examine the impact of a restrictive vs. liberal transfusion strategy on arterial lactate and oxygen content differences in children with single-ventricle physiology post cavopulmonary connection. Children with single-ventricle physiology are routinely transfused postoperatively to increase systemic oxygen delivery, and transfusion thresholds in this population have not been studied.
DESIGN: Prospective, randomized, controlled, clinical trial.
SETTING: Pediatric cardiac intensive care unit in a teaching hospital.
PATIENTS: Infants and children (n = 60) with variations of single-ventricle physiology presenting for cavopulmonary connection.
INTERVENTIONS: Subjects were randomized to a restrictive (hemoglobin of < 9.0 g/dL), or liberal (hemoglobin of ≥ 13.0 g/dL) transfusion strategy for 48 hrs post operation. Primary outcome measures were mean and peak arterial lactate. Secondary end points were arteriovenous (C(a-v)o2) and arteriocerebral oxygen content (C(a-c)o2) differences and clinical outcomes.
MEASUREMENTS AND MAIN RESULTS: A total of 30 children were in each group. There were no significant preoperative differences. Mean hemoglobin in the restrictive and liberal groups were 11 ± 1.3 g/dL and 13.9 ± 0.5 g/dL, respectively (p < .01). No differences in mean (1.4 ± 0.5 mmol/L [Restrictive] vs. 1.4 ± 0.4 mmol/L [Liberal]) or peak (3.1 ± 1.5 mmol/L [Restrictive] vs. 3.2 ± 1.3 mmol/L [Liberal]) lactate between groups were found. Mean number of red blood cell transfusions were 0.43 ± 0.6 and 2.1 ± 1.2 (p < .01), and donor exposure was 1.2 ± 0.7 and 2.4 ± 1.1 to (p < .01), for each group, respectively. No differences were found in C(a-v)o2, C(a-c)o2, or clinical outcome measures.
CONCLUSION: Children with single-ventricle physiology do not benefit from a liberal transfusion strategy after cavopulmonary connection. A restrictive red blood cell transfusion strategy decreases the number of transfusions, donor exposures, and potential risks in these children. Larger studies with clinical outcome measures are needed to determine the transfusion threshold for children post cardiac repair or palliation for congenital heart disease.

PMID 20495502
J A Carcillo, A L Davis, A Zaritsky
Role of early fluid resuscitation in pediatric septic shock.
JAMA. 1991 Sep 4;266(9):1242-5.
Abstract/Text OBJECTIVE: To examine the association of the volume of fluid administered at 1 and 6 hours after presentation, with survival and the occurrence of the adult respiratory distress syndrome, cardiogenic pulmonary edema, and persistent hypovolemia during the resuscitation of children with septic shock.
SETTING AND PATIENTS: All pediatric patients with septic shock presenting to the emergency department over a 6-year period and having a pulmonary artery catheter inserted by 6 hours after presentation were identified.
METHODS: Patients were analyzed together and in three groups based on fluid volume in the first hour: group 1, less than 20 mL/kg; group 2, 20 to 40 mL/kg; and group 3, more than 40 mL/kg. Adult respiratory distress syndrome was diagnosed by the presence of alveolar infiltrates, hypoxemia, and a pulmonary capillary wedge pressure of 15 mm Hg or less. Cardiogenic pulmonary edema was diagnosed similarly, except the pulmonary capillary wedge pressure was greater than 15 mm Hg. Hypovolemia was diagnosed by the presence of oliguria, hypotension, and a pulmonary capillary wedge pressure of 8 mm Hg or less 6 hours after presentation.
RESULTS: We identified 34 patients (median age, 13.5 months). At 1 and 6 hours, respectively, group 1 (n = 14) received 11 +/- 6 and 71 +/- 29 mL/kg (mean +/- SD) of fluid; group 2 received 32 +/- 5 and 108 +/- 54 mL/kg of fluid; and group 3 received 69 +/- 19 and 117 +/- 29 mL/kg of fluid. Survival in group 3 (eight of nine patients) was significantly better than in group 1 (six of 14 patients) or group 2 (four of 11 patients). Adult respiratory distress syndrome developed in 11 patients (32%) and cardiogenic pulmonary edema developed in five patients (15%). Having adult respiratory distress syndrome was associated with increased mortality, but adult respiratory distress syndrome was not increased in any group. Similarly, cardiogenic pulmonary edema was not associated with the fluid volume received or with decreased survival. Hypovolemia occurred in six patients in group 1 and two patients in group 2; all eight subsequently died.
CONCLUSION: Rapid fluid resuscitation in excess of 40 mL/kg in the first hour following emergency department presentation was associated with improved survival, decreased occurrence of persistent hypovolemia, and no increase in the risk of cardiogenic pulmonary edema or adult respiratory distress syndrome in this group of pediatric patients with septic shock.

PMID 1870250
Samuel Akech, Hannah Ledermann, Kathryn Maitland
Choice of fluids for resuscitation in children with severe infection and shock: systematic review.
BMJ. 2010 Sep 2;341:c4416. Epub 2010 Sep 2.
Abstract/Text OBJECTIVE: To systemically review the evidence from clinical trials comparing the use of crystalloids and colloids for fluid resuscitation in children with severe infection.
DATA SOURCES: Medline (1950-2008), PubMed, the Cochrane Library, Embase (1980-2008), and reference lists. Eligibility criteria Published studies comparing fluid resuscitation with crystalloid or colloidal solutions in severe infectious illness in children aged >1 month to MAIN OUTCOME MEASURES: Efficacy in the treatment of shock, mortality, and reported adverse events.
RESULTS: Nine trials fulfilled criteria, eight of which compared crystalloids with colloids. All trials were conducted in settings with poor resources and predominantly included patients with malaria or dengue haemorrhagic shock. None of the trials had mortality as a primary outcome. Three out of six studies that reported at least one death showed better survival in children resuscitated with colloids compared with crystalloids (Peto fixed odds ratio ranging from 0.18 (95% confidence interval 0.02 to 1.42) to 0.48 (0.06 to 3.99)). Studies contributing data on mortality had some methodological limitations so caution is recommended when interpreting this finding. Studies were heterogeneous so combined estimates were not calculated. The review was limited by inclusion of only published studies.
CONCLUSIONS: The current evidence on choice of fluids for resuscitation in children with infections is weak. While existing trials have provided important evidence in malaria and dengue, resuscitation in children with paediatric sepsis, for which colloids could theoretically be of benefit, has not been studied. The evidence from existing studies is not robust enough to make any definitive recommendations over the choice of resuscitation fluid and a definitive trial is required to address this.

PMID 20813823
Peter Hicks, D James Cooper, Australian and New Zealand Intensive Care Society (ANZICS) Board and Clinical Trials Group Executive Committee
The Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008.
Crit Care Resusc. 2008 Mar;10(1):8.
Abstract/Text
PMID 18304010
INIS Collaborative Group, Peter Brocklehurst, Barbara Farrell, Andrew King, Edmund Juszczak, Brian Darlow, Khalid Haque, Alison Salt, Ben Stenson, William Tarnow-Mordi
Treatment of neonatal sepsis with intravenous immune globulin.
N Engl J Med. 2011 Sep 29;365(13):1201-11. doi: 10.1056/NEJMoa1100441.
Abstract/Text BACKGROUND: Neonatal sepsis is a major cause of death and complications despite antibiotic treatment. Effective adjunctive treatments are needed. Newborn infants are relatively deficient in endogenous immunoglobulin. Meta-analyses of trials of intravenous immune globulin for suspected or proven neonatal sepsis suggest a reduced rate of death from any cause, but the trials have been small and have varied in quality.
METHODS: At 113 hospitals in nine countries, we enrolled 3493 infants receiving antibiotics for suspected or proven serious infection and randomly assigned them to receive two infusions of either polyvalent IgG immune globulin (at a dose of 500 mg per kilogram of body weight) or matching placebo 48 hours apart. The primary outcome was death or major disability at the age of 2 years.
RESULTS: There was no significant between-group difference in the rates of the primary outcome, which occurred in 686 of 1759 infants (39.0%) who received intravenous immune globulin and in 677 of 1734 infants (39.0%) who received placebo (relative risk, 1.00; 95% confidence interval, 0.92 to 1.08). Similarly, there were no significant differences in the rates of secondary outcomes, including the incidence of subsequent sepsis episodes. In follow-up of 2-year-old infants, there were no significant differences in the rates of major or nonmajor disability or of adverse events.
CONCLUSIONS: Therapy with intravenous immune globulin had no effect on the outcomes of suspected or proven neonatal sepsis.

PMID 21962214
Ryan Van Wert, Jan O Friedrich, Damon C Scales, Ron Wald, Neill K J Adhikari, University of Toronto Acute Kidney Injury Research Group
High-dose renal replacement therapy for acute kidney injury: Systematic review and meta-analysis.
Crit Care Med. 2010 May;38(5):1360-9. doi: 10.1097/CCM.0b013e3181d9d912.
Abstract/Text OBJECTIVE: To determine the effect of renal replacement therapy dose on mortality and dialysis dependence in patients with acute kidney injury.
DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials to October 2009; PubMed "Related Articles;" bibliographies of included trials; and additional information from trial authors.
STUDY SELECTION: Randomized and quasi-randomized, controlled trials in adults with acute kidney injury prescribed highvs. standard-dose continuous renal replacement therapy (> or =30 mL/kg/hr vs. <30 mL/kg/hr), intermittent hemodialysis, or sustained low-efficiency dialysis (daily vs. alternate day, or by target biochemistry).
DATA EXTRACTION: Three authors independently selected studies and extracted data on outcomes and study quality. Meta-analyses used random-effects models.
DATA SYNTHESIS: Of 5416 citations, 12 trials (n = 3999) met inclusion criteria. Modalities included continuous renal replacement therapy (7 trials), intermittent hemodialysis (3 trials), sustained low-efficiency dialysis (1 trial), and all three (1 trial). Study quality was moderate-high. Meta-analyses found no effect of high-dose renal replacement therapy on mortality (risk ratio, 0.89; 95% confidence interval, 0.77-1.03; 12 trials; n = 3954) or dialysis dependence among survivors (risk ratio, 1.15; 95% confidence interval, 0.92-1.44; 8 trials with events; n = 1743). The effect on mortality was similar (all interaction p values were nonsignificant) in patients with sepsis (risk ratio, 1.02; 95% confidence interval, 0.85-1.23; 9 trials; n = 1786) vs. without sepsis (risk ratio, 0.89; 95% confidence interval, 0.75-1.05; 8 trials; n = 1955), treated exclusively with continuous renal replacement therapy (risk ratio, 0.87; 95% confidence interval, 0.71-1.06; 7 trials; n = 2462) vs. other modalities alone or in combination (risk ratio, 0.92; 95% confidence interval, 0.70 -1.21; 5 trials; n = 1492), and in trials with low (risk ratio, 0.96; 95% confidence interval, 0.85-1.09; 6 trials; n = 3475) vs. higher (risk ratio, 0.76; 95% confidence interval, 0.53-1.09; 6 trials; n = 479) risk of bias.
CONCLUSIONS: High-dose renal replacement therapy in acute kidney injury does not improve patient survival or recovery of renal function overall or in important patient subgroups, including those with sepsis.

PMID 20308884
Kiran B Hebbar, Jana A Stockwell, Traci Leong, James D Fortenberry
Incidence of adrenal insufficiency and impact of corticosteroid supplementation in critically ill children with systemic inflammatory syndrome and vasopressor-dependent shock.
Crit Care Med. 2011 May;39(5):1145-50. doi: 10.1097/CCM.0b013e31820eb4e4.
Abstract/Text INTRODUCTION: Adrenal insufficiency may be common in adults and children with vasopressor-resistant shock. We developed a protocolized approach to low-dose adrenocorticotropin testing and empirical low-dose glucocorticoid/mineralocorticoid supplementation in children with systemic inflammatory response syndrome and persistent hypotension following fluid resuscitation and vasopressor infusion.
HYPOTHESIS: We hypothesized that absolute and relative adrenal insufficiency was common in children with systemic inflammatory response syndrome requiring vasopressor support and that steroid administration would be associated with decreased vasopressor need.
METHODS: Retrospective review of pediatric patients with systemic inflammatory response syndrome and vasopressor-dependent shock receiving protocol-based adrenocorticotropin testing and low-dose steroid supplementation. The incidence of absolute and relative adrenal insufficiency was determined using several definitions. Vasopressor dose requirements were evaluated before, and following, initiation of corticosteroids.
RESULTS: Seventy-eight patients met inclusion criteria for systemic inflammatory response syndrome and shock; 40 had septic shock. Median age was 84 months (range, 0.5-295). By adrenocorticotropin testing, 44 (56%) had absolute adrenal insufficiency, 39 (50%) had relative adrenal insufficiency, and 69 (88%) had either form of adrenal insufficiency. Adrenal insufficiency incidence was significantly higher in children >2 yrs (p = .0209). Therapeutic interventions included median 80-mL/kg fluid resuscitation; 65% of patients required dopamine, 58% norepinephrine, and 49% dopamine plus norepinephrine. With steroid supplementation, median dopamine dose decreased from 10 to 4 μg/kg/min at 4 hrs (p = .0001), and median dose of norepinephrine decreased from 0.175 μg/kg/min to 0.05 μg/kg/min at 4 hrs (p = .039).
CONCLUSIONS: Absolute and relative adrenal insufficiency was prevalent in this cohort of children with systemic inflammatory response syndrome and vasopressor-dependent shock and increased with age. Introduction of steroids produced a significant reduction in vasopressor duration and dosage. Use of low-dose adrenocorticotropin testing may help further delineate populations who require steroid supplementation.

PMID 21336126
Oliver Karam, Marisa Tucci, Thierry Ducruet, Heather Anne Hume, Jacques Lacroix, France Gauvin, Canadian Critical Care Trials Group, PALISI Network
Red blood cell transfusion thresholds in pediatric patients with sepsis.
Pediatr Crit Care Med. 2011 Sep;12(5):512-8. doi: 10.1097/PCC.0b013e3181fe344b.
Abstract/Text OBJECTIVES: In children with severe sepsis or septic shock, the optimal red blood cell transfusion threshold is unknown. We analyzed the subgroup of patients with sepsis and transfusion requirements in a pediatric intensive care unit study to determine the impact of a restrictive vs. liberal transfusion strategy on clinical outcome.
DESIGN: Subgroup analysis of a prospective, multicenter, randomized, controlled trial.
SETTING: Multicenter pediatric critical care units.
PATIENTS: Stabilized critically ill children (mean systemic arterial pressure >2 sd below normal mean for age and cardiovascular support not increased for at least 2 hrs before enrollment) with a hemoglobin ≤ 9.5 g/dL within 7 days after pediatric critical care unit admission.
INTERVENTIONS: One hundred thirty-seven stabilized critically ill children with sepsis were randomized to receive red blood cell transfusion if their hemoglobin decreased to either <7.0 g/dL (restrictive group) or 9.5 g/dL (liberal group).
MEASUREMENTS AND MAIN RESULTS: In the restrictive group (69 patients), 30 patients did not receive any red blood cell transfusion, whereas only one patient in the liberal group (68 patients) never underwent transfusion (p < .01). No clinically significant differences were found for the occurrence of new or progressive multiple organ dysfunction syndrome (18.8% vs. 19.1%; p = .97), for pediatric critical care unit length of stay (p = .74), or for pediatric critical care unit mortality (p = .44) in the restrictive vs. liberal group.
CONCLUSIONS: In this subgroup analysis of children with stable sepsis, we found no evidence that a restrictive red cell transfusion strategy, as compared to a liberal one, increased the rate of new or progressive multiple organ dysfunction syndromes. Furthermore, a restrictive transfusion threshold significantly reduced exposure to blood products. Our data suggest that a hemoglobin level of 7.0 g/dL may be safe stabilized for children with sepsis, but further studies are required to support this recommendation.

PMID 21057356
Cláudio F de Oliveira, Débora S F de Oliveira, Adriana F C Gottschald, Juliana D G Moura, Graziela A Costa, Andréa C Ventura, José Carlos Fernandes, Flávio A C Vaz, Joseph A Carcillo, Emanuel P Rivers, Eduardo J Troster
ACCM/PALS haemodynamic support guidelines for paediatric septic shock: an outcomes comparison with and without monitoring central venous oxygen saturation.
Intensive Care Med. 2008 Jun;34(6):1065-75. doi: 10.1007/s00134-008-1085-9. Epub 2008 Mar 28.
Abstract/Text INTRODUCTION: The ACCM/PALS guidelines address early correction of paediatric septic shock using conventional measures. In the evolution of these recommendations, indirect measures of the balance between systemic oxygen delivery and demands using central venous or superior vena cava oxygen saturation (ScvO(2) > or = 70%) in a goal-directed approach have been added. However, while these additional goal-directed endpoints are based on evidence-based adult studies, the extrapolation to the paediatric patient remains unvalidated.
OBJECTIVE: The purpose of this study was to compare treatment according to ACCM/PALS guidelines, performed with and without ScvO(2) goal-directed therapy, on the morbidity and mortality rate of children with severe sepsis and septic shock. DESIGN, PARTICIPANTS AND INTERVENTIONS: Children and adolescents with severe sepsis or fluid-refractory septic shock were randomly assigned to ACCM/PALS with or without ScvO(2) goal-directed resuscitation.
MEASUREMENTS: Twenty-eight-day mortality was the primary endpoint.
RESULTS: Of the 102 enrolled patients, 51 received ACCM/PALS with ScvO(2) goal-directed therapy and 51 received ACCM/PALS without ScvO(2) goal-directed therapy. ScvO(2) goal-directed therapy resulted in less mortality (28-day mortality 11.8% vs. 39.2%, p=0.002), and fewer new organ dysfunctions (p=0.03). ScvO(2) goal-directed therapy resulted in more crystalloid (28 (20-40) vs. 5 (0-20 ml/kg, p<0.0001), blood transfusion (45.1% vs. 15.7%, p=0.002) and inotropic (29.4% vs. 7.8%, p=0.01) support in the first 6 h.
CONCLUSIONS: This study supports the current ACCM/PALS guidelines. Goal-directed therapy using the endpoint of a ScvO(2)> or =70% has a significant and additive impact on the outcome of children and adolescents with septic shock.

PMID 18369591

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