Extremely early initiation of vasopressors might not decrease short-term mortality for adults with septic shock: a systematic review and meta-analysis

Annals of Intensive Care volume 15, Article number: 18 (2025)

Published: 27 January 2025

Background

The optimal timing for initiating vasopressor therapy in patients with septic shock remains unclear. This study aimed to assess the impact of early versus late vasopressor initiation on clinical outcomes.

Methods

A systematic review and meta-analysis were conducted by searching PubMed, Embase, and Cochrane databases. Studies comparing early and late vasopressor administration in septic shock patients were included. The primary outcome was short-term mortality, and subgroup analyses were performed based on different initiation timings.

Results

Eleven studies with 6,661 patients were included. Different studies define the ‘early administration’ timeframe variously, ranging from one to seven hours. No significant difference in short-term mortality was observed between early and late administration in the combined analysis of 3,757 patients from two RCTs and three quasi-experimental studies (OR: 0.66, 95% CI: [0.36, 1.19], I²: 82%). However, lower mortality was found in subgroups with early but not extremely early initiation (one to three hours, OR: 0.70, 95% CI: [0.60, 0.82], I²: 0%), and those using septic shock diagnosis as time zero (OR: 0.64, 95% CI: [0.48, 0.85], I²: 39%).

Conclusion

Our findings found that earlier initiation of vasopressor therapy, particularly within one to three hours after the diagnosis of septic shock, may be associated with reduced short-term mortality in certain subgroups. However, due to the heterogeneity in study definitions and potential confounding factors, these results should be interpreted cautiously. Further standardized investigations are warranted to precisely determine the optimal timing for vasopressor initiation to maximize survival outcomes in patients with septic shock.

 

Sex disparities in ICU care and outcomes after cardiac arrest: a Swiss nationwide analysis

Critical Care volume 29, Article number: 42 (2025) 

Published: 23 January 2025

Background

Conflicting data exist regarding sex-specific outcomes after cardiac arrest. This study investigates sex disparities in the provision of critical care and outcomes of in-hospital (IHCA) and out-of-hospital cardiac arrest (OHCA) patients.

Methods

Analysis of adult cardiac arrest patients admitted to certified Swiss intensive care units (ICUs) (01/2008–12/2022) using the nationwide prospective ICU registry. The primary outcome was ICU mortality, with secondary outcomes including ICU admission probability and advanced treatment provision.

Results

Among 41,733 individuals (34.9% women), 21,692 patients (30.6% women) were admitted to ICUs (16,571 OHCA patients/5121 IHCA patients). Women were less likely to be admitted to the ICU than men (incidence rate ratio 0.82 [95% CI 0.80–0.85] and had a higher ICU mortality (41.8% vs 36.2%; p < 0.001). Mortality differences were more pronounced in OHCA patients (unadjusted HR: 1.35 [95% CI 1.28–1.43]; adjusted HR: 1.19 [95% CI 1.12–1.25]). In IHCA patients, mortality differences were less pronounced (unadjusted HR: 1.14 [95% CI 1.04–1.25]) and vanished after adjustment for confounders: adjusted HR: 1.03 [95% CI 0.94–1.13]). Women after cardiac arrest were older, more severely ill, and received fewer interventions before (44.7% vs 54.0%; p < 0.001) and during ICU stay. A subgroup analysis of 11,202 patients revealed that treatment limitations were more frequent in women (46.7% vs 38.7%; p < 0.001). However, these limitations were associated with an increased risk of death in both sexes.

Conclusions

This study highlights sex disparities in short-term mortality and ICU resource allocation among cardiac arrest patients, with women potentially facing disadvantages, in particular after OHCA. The limitations of ICU registry data, particularly the lack of detailed cardiac arrest-specific and comorbidity information, restrict definitive conclusions. Future research should prioritize prospective studies with more granular data to better understand and address these disparities.

 

Out-of-hospital cardiac arrest in children: an epidemiological study based on the German Resuscitation Registry identifying modifiable factors for return of spontaneous circulation

 

by Stephan Katzenschlager, Inga K. Kelpanides, Patrick Ristau, Matthias Huck, Stephan Seewald, Sebastian Brenner, Florian Hoffmann, Jan Wnent, Jo Kramer-Johansen, Ingvild B. M. Tjelmeland, Markus A. Weigand, Jan-Thorsten Gräsner and Erik Popp 

 

Critical Care volume 27, Article number: 349 (2023)

 

Aim

This work provides an epidemiological overview of out-of-hospital cardiac arrest (OHCA) in children in Germany between 2007 and 2021. We wanted to identify modifiable factors associated with survival.

Methods

Data from the German Resuscitation Registry (GRR) were used, and we included patients registered between 1st January 2007 and 31st December 2021. We included children aged between > 7 days and 17 years, where cardiopulmonary resuscitation (CPR) was started, and treatment was continued by emergency medical services (EMS). Incidences and descriptive analyses are presented for the overall cohort and each age group. Multivariate binary logistic regression was performed on the whole cohort to determine the influence of (1) CPR with/without ventilation started by bystander, (2) OHCA witnessed status and (3) night-time on the outcome hospital admission with return of spontaneous circulation (ROSC).

Results

OHCA in children aged < 1 year had the highest incidence of the same age group, with 23.42 per 100 000. Overall, hypoxia was the leading presumed cause of OHCA, whereas trauma and drowning accounted for a high proportion in children aged > 1 year. Bystander-witnessed OHCA and bystander CPR rate were highest in children aged 1–4 years, with 43.9% and 62.3%, respectively. In reference to EMS-started CPR, bystander CPR with ventilation were associated with an increased odds ratio for ROSC at hospital admission after adjusting for age, sex, year of OHCA and location of OHCA.

Conclusion

This study provides an epidemiological overview of OHCA in children in Germany and identifies bystander CPR with ventilation as one primary factor for survival.

Cardiovascular determinants of resuscitation from sepsis and septic shock

Cardiovascular determinants of resuscitation from sepsis and septic shock

By Fabio Guarracino, Pietro Bertini and Michael R. Pinsky  

Critical Care: 201923:118

Background: We hypothesized that the cardiovascular responses to Surviving Sepsis Guidelines (SSG)-defined resuscitation are predictable based on the cardiovascular state.

Methods: Fifty-five septic patients treated by SSG were studied before and after volume expansion (VE), and if needed norepinephrine (NE) and dobutamine. We measured mean arterial pressure (MAP), cardiac index (CI), and right atrial pressure (Pra) and calculated pulse pressure and stroke volume variation (PPV and SVV), dynamic arterial elastance (Ea_dyn), arterial elastance (Ea) and left ventricular (LV) end-systolic elastance (Ees), Ees/Ea (VAC), LV ejection efficiency (LVeff), mean systemic pressure analogue (Pmsa), venous return pressure gradient (Pvr), and cardiac performance (Eh), using standard formulae.

Results: All patients were hypotensive (MAP 56.8 ± 3.1 mmHg) and tachycardic (113.1 ± 7.5 beat min⁻¹), with increased lactate levels (lactate = 5.0 ± 4.2 mmol L⁻¹) with a worsened VAC. CI was variable but > 2 L min⁻¹ M⁻² in 74%. Twenty-eight-day mortality was 48% and associated with admission lactate, blood urea nitrogen (BUN), and creatinine levels but not cardiovascular state. In all patients, both MAP and CI improved following VE, as well as cardiac contractility (Ees). Fluid administration improved Pra, Pmsa, and Pvr in all patients, whereas both HR and Ea decreased after VE, thus normalizing VAC. CI increases were proportional to baseline PPV and SVV. CI increases proportionally decreased PPV and SVV. VE increased MAP > 65 mmHg in 35/55 patients. MAP responders had higher PPV, SVV, and Ea_dyn than non-responders. NE was given to 20/55 patients in septic shock, but increased MAP > 65 mmHg in only 12. NE increased Ea, Ea_dyn, Pra, Pmsa, and VAC while decreasing HR, PPV, SVV, and LVeff. MAP responders had higher pre-NE Ees and lower VAC. Dobutamine was given to 6/8 patients who remained hypotensive following NE. It increased Ees, MAP, CI, and LVeff, while decreasing HR, Pra, and VAC. At all times and all steps of the protocol, CI changes were proportional to Pvr changes independent of treatment.

Conclusions: The cardiovascular response to SSG-based resuscitation is highly heterogeneous but predictable from pre-treatment measures of cardiovascular state.

Female Physician Leadership During Cardiopulmonary Resuscitation Is Associated With Improved Patient Outcomes*

Female Physician Leadership During Cardiopulmonary Resuscitation Is Associated With Improved Patient Outcomes*

by Meier, Angela; Yang, Jenny; Liu, Jinyuan; Beitler, Jeremy R.; Tu, Xin M.; Owens, Robert L.; Sundararajan, Radhika L.; Malhotra, Atul; Sell, Rebecca E.  

Critical Care Medicine: January 2019 - Volume 47 - Issue 1 - p e8–e13

Objectives: A recently published simulation study suggested that women are inferior leaders of cardiopulmonary resuscitation efforts. The aim of this study was to compare female and male code leaders in regard to cardiopulmonary resuscitation outcomes in a real-world clinical setting.

Design: Retrospective cohort review. Setting: Two academic, urban hospitals in San Diego, California. Subjects: One-thousand eighty-two adult inpatients who suffered cardiac arrest and underwent cardiopulmonary resuscitation. Interventions: None.

Measurements and Main Results: We analyzed whether physician code leader gender was independently associated with sustained return of spontaneous circulation and survival to discharge and with markers of quality cardiopulmonary resuscitation. Of all arrests, 327 (30.1%) were run by female physician code leaders with 251 (76.8%) obtaining return of spontaneous circulation, and 122 (37.3%) surviving to discharge. Male physicians ran 757 codes obtaining return of spontaneous circulation in 543 (71.7%) with 226 (29.9%) surviving to discharge. When adjusting for variables, female physician code leader gender was independently associated with a higher likelihood of return of spontaneous circulation (odds ratio, 1.36; 95% CI, 1.01–1.85; p = 0.049) and survival to discharge (odds ratio, 1.53; 95% CI, 1.15–2.02; p < 0.01). Additionally, the odds ratio for survival to discharge was 1.62 (95% CI, 1.13–2.34; p < 0.01) for female physicians with a female code nurse when compared with male physician code leaders paired with a female code nurse. Gender of code leader was not associated with cardiopulmonary resuscitation quality.

Conclusions: In contrast to data derived from a simulated setting with medical students, real life female physician leadership of cardiopulmonary resuscitation is not associated with inferior outcomes. Appropriately, trained physicians can lead high-quality cardiopulmonary resuscitation irrespective of gender.

Protocol-Based Resuscitation Bundle to Improve Outcomes in Septic Shock Patients: Evaluation of the Michigan Health and Hospital Association Keystone Sepsis Collaborative

Protocol-Based Resuscitation Bundle to Improve Outcomes in Septic Shock Patients: Evaluation of the Michigan Health and Hospital Association Keystone Sepsis Collaborative
Critical Care Medicine: December 2016 - Volume 44 - Issue 12 - p 2123–2130
Thompson, M et al

Objectives: To evaluate the impact of a multi-ICU quality improvement collaborative implementing a protocol-based resuscitation bundle to treat septic shock patients. 
Design: A difference-in-differences analysis compared patient outcomes in hospitals participating in the Michigan Health & Hospital Association Keystone Sepsis collaborative (n = 37) with noncollaborative hospitals (n = 50) pre- (2010–2011) and postimplementation (2012–2013). Collaborative hospitals were also stratified as high (n = 19) and low (n = 18) adherence based on their overall bundle adherence. 
Setting: Eighty-seven Michigan hospitals with ICUs. Patients: We compared 22,319 septic shock patients in collaborative hospitals compared to 26,055 patients in noncollaborative hospitals using the Michigan Inpatient Database. Interventions: Multidisciplinary ICU teams received informational toolkits, standardized screening tools, and continuous quality improvement, aided by cultural improvement. 
Measurements and Main Results: In-hospital mortality and hospital length of stay significantly improved between pre- and postimplementation periods for both collaborative and noncollaborative hospitals. Comparing collaborative and noncollaborative hospitals, we found no additional reductions in mortality (odds ratio, 0.94; 95% CI, 0.87–1.01; p = 0.106) or length of stay (–0.3 d; 95% CI, –0.7 to 0.1 d; p = 0.174). Compared to noncollaborative hospitals, high adherence hospitals had significant reductions in mortality (odds ratio, 0.84; 95% CI, 0.79–0.93; p < 0.001) and length of stay (–0.7 d; 95% CI, –1.1 to –0.2; p < 0.001), whereas low adherence hospitals did not (odds ratio, 1.07; 95% CI, 0.97–1.19; p = 0.197; 0.2 d; 95% CI, –0.3 to 0.8; p = 0.367). Conclusions: Participation in the Keystone Sepsis collaborative was unable to improve patient outcomes beyond concurrent trends. High bundle adherence hospitals had significantly greater improvements in outcomes, but further work is needed to understand these findings.

Cerebral Oximetry During Cardiac Arrest: A Multicenter Study of Neurologic Outcomes and Survival

Cerebral Oximetry During Cardiac Arrest: A Multicenter Study of Neurologic Outcomes and Survival

Critical Care Medicine:

September 2016 - Volume 44 - Issue 9 - p 1663–1674

 Parnia, Sam et alObjectives: Cardiac arrest is associated with morbidity and mortality because of cerebral ischemia. Therefore, we tested the hypothesis that higher regional cerebral oxygenation during resuscitation is associated with improved return of spontaneous circulation, survival, and neurologic outcomes at hospital discharge. We further examined the validity of regional cerebral oxygenation as a test to predict these outcomes. Design: Multicenter prospective study of in-hospital cardiac arrest. Setting: Five medical centers in the United States and the United Kingdom. Patients: Inclusion criteria are as follows: in-hospital cardiac arrest, age 18 years old or older, and prolonged cardiopulmonary resuscitation greater than or equal to 5 minutes. Patients were recruited consecutively during working hours between August 2011 and September 2014. Survival with a favorable neurologic outcome was defined as a cerebral performance category 1–2. Interventions: Cerebral oximetry monitoring. Measurements and Main Results: Among 504 in-hospital cardiac arrest events, 183 (36%) met inclusion criteria. Overall, 62 of 183 (33.9%) achieved return of spontaneous circulation, whereas 13 of 183 (7.1%) achieved cerebral performance category 1–2 at discharge. Higher mean ± SD regional cerebral oxygenation was associated with return of spontaneous circulation versus no return of spontaneous circulation (51.8% ± 11.2% vs 40.9% ± 12.3%) and cerebral performance category 1–2 versus cerebral performance category 3–5 (56.1% ± 10.0% vs 43.8% ± 12.8%) (both p < 0.001). Mean regional cerebral oxygenation during the last 5 minutes of cardiopulmonary resuscitation best predicted the return of spontaneous circulation (area under the curve, 0.76; 95% CI, 0.69–0.83); regional cerebral oxygenation greater than or equal to 25% provided 100% sensitivity (95% CI, 94–100) and 100% negative predictive value (95% CI, 79–100); regional cerebral oxygenation greater than or equal to 65% provided 99% specificity (95% CI, 95–100) and 93% positive predictive value (95% CI, 66–100) for return of spontaneous circulation. Time with regional cerebral oxygenation greater than 50% during cardiopulmonary resuscitation best predicted cerebral performance category 1–2 (area under the curve, 0.79; 95% CI, 0.70–0.88). Specifically, greater than or equal to 60% cardiopulmonary resuscitation time with regional cerebral oxygenation greater than 50% provided 77% sensitivity (95% CI,:46–95), 72% specificity (95% CI, 65–79), and 98% negative predictive value (95% CI, 93–100) for cerebral performance category 1–2. Conclusions: Cerebral oximetry allows real-time, noninvasive cerebral oxygenation monitoring during cardiopulmonary resuscitation. Higher cerebral oxygenation during cardiopulmonary resuscitation is associated with return of spontaneous circulation and neurologically favorable survival to hospital discharge. Achieving higher regional cerebral oxygenation during resuscitation may optimize the chances of cardiac arrest favorable outcomes.

Early goal-directed resuscitation of patients with septic shock: current evidence and future directions

Early goal-directed resuscitation of patients with septic shock: current evidence and future directions
Critical Care 2015, 19:286  doi:10.1186/s13054-015-1011-9

Gupta, R, et al

Severe sepsis and septic shock are among the leading causes of mortality in the intensive care unit. Over a decade ago, early goal-directed therapy (EGDT) emerged as a novel approach for reducing sepsis mortality and was incorporated into guidelines published by the international Surviving Sepsis Campaign. In addition to requiring early detection of sepsis and prompt initiation of antibiotics, the EGDT protocol requires invasive patient monitoring to guide resuscitation with intravenous fluids, vasopressors, red cell transfusions, and inotropes. The effect of these measures on patient outcomes, however, remains controversial. Recently, three large randomized trials were undertaken to re-examine the effect of EGDT on morbidity and mortality: the ProCESS trial in the United States, the ARISE trial in Australia and New Zealand, and the ProMISe trial in England. These trials showed that EGDT did not significantly decrease mortality in patients with septic shock compared with usual care. In particular, whereas early administration of antibiotics appeared to increase survival, tailoring resuscitation to static measurements of central venous pressure and central venous oxygen saturation did not confer survival benefit to most patients. In the following review, we examine these findings as well as other evidence from recent randomized trials of goal-directed resuscitation. We also discuss future areas of research and emerging paradigms in sepsis trials.

Trial of early, goal-directed resuscitation for septic shock

Trial of early, goal-directed resuscitation for septic shock. NEJM, March 2015

Mouncey, P.R., et al.

http://www.nejm.org/doi/full/10.1056/NEJMoa1500896#t=article

The incidence of severe sepsis and septic shock in adults is estimated to range from 56 to 91 per 100,000 population per year. Affected patients have high rates of death, complications, and resource utilization.

Goal-directed resuscitation for patients with early septic shock

Goal-directed resuscitation for patients with early septic shock. NEJM, October 2014 [online]

The ARISE Investigators and the ANZICS Clinical Trials Group

http://www.nejm.org/doi/full/10.1056/NEJMoa1404380?af=R&rss=currentIssue

Early goal-directed therapy  has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting to the emergency department with septic shock. However, its effectiveness is uncertain.

Critical Care: 12March - 10 April

Review Clinical review: Airway hygiene in the intensive care unit
Jelic S, Cunningham J, Factor PCritical Care, 2008 12:209 ( 31 March 2008 )
[Abstract][Full text] [PDF]

Review Clinical review: Medication errors in critical care
Moyen E, Camiré E, Stelfox HCritical Care, 2008 12:208 ( 12 March 2008 )
[Abstract][Full text] [PDF] [PubMed]

Commentary Patient-level glucose reporting: averages, episodes, or something in between? Braithwaite SCritical Care, 2008 12:133 ( 10 April 2008 ) [PDF]

Commentary Vasopressin in vasodilatory shock: is the heart in danger?
Hauser B, Asfar P, Calzia E, Laporte R, Georgieff M, Radermacher PCritical Care, 2008 12:132 ( 10 April 2008 ) [PDF]

Commentary Delirium assessment in the intensive care unit: patient population matters
Pisani MCritical Care, 2008 12:131 ( 7 April 2008 ) [Abstract][Full text] [PDF]

Commentary The pursuit of a high central venous oxygen saturation in sepsis: growing concerns Bellomo R, Reade M, Warrillow SCritical Care, 2008 12:130 ( 7 April 2008 )
[Abstract][Full text] [PDF]

Commentary Myocardial infarction on the ICU: can we do better?
Webb I, Coutts JCritical Care, 2008 12:129 ( 3 April 2008 )
[Abstract][Full text] [PDF] [PubMed]

Commentary Tracheostomy decannulation: marathons and finish lines
Heffner JCritical Care, 2008 12:128 ( 31 March 2008 )
[Abstract][Full text] [PDF] [PubMed]

Commentary Pulmonary artery occlusion pressure estimation by transesophageal echocardiography: is simpler better?
Voga GCritical Care, 2008 12:127 ( 31 March 2008 )
[Abstract][Full text] [PDF] [PubMed]

Commentary Circulating pro-apoptotic mediators in burn septic acute renal failure Oudemans-van Straaten HCritical Care, 2008 12:126 ( 31 March 2008 )
[Abstract][Full text] [PDF] [PubMed]

Commentary Knowing who would respond to a recruitment maneuver before actually doing it – this might be a way to go
Kuhlen RCritical Care, 2008 12:125 ( 31 March 2008 )
[Abstract][Full text] [PDF] [PubMed]

Commentary Insulin, intracerebral glucose and bedside biochemical monitoring utilizing microdialysis
Nordström CCritical Care, 2008 12:124 ( 31 March 2008 ) [PDF]

Commentary Optimal vasopressor drug therapy during resuscitation
Ornato JCritical Care, 2008 12:123 ( 31 March 2008 )
[Abstract][Full text] [PDF] [PubMed]

Commentary Lost in translation? The pursuit of lung-protective ventilation
Jones ACritical Care, 2008 12:122 ( 31 March 2008 ) [PDF]

Commentary KL-6 in acute lung injury: will it leave its mark?
Shyamsundar M, McAuley DCritical Care, 2008 12:121 ( 31 March 2008 ) [PDF]

Commentary Recently published papers: Sepsis – guidelines, treatment and novel approaches Kalsi N, Forni LCritical Care, 2008 12:120 ( 31 March 2008 ) [Abstract] [Full text] [PDF]

Commentary Towards goal-directed therapy of hepatorenal syndrome: we have the tools but we need the trials
Mookerjee R, Jalan RCritical Care, 2008 12:119 ( 19 March 2008 )
[Abstract][Full text] [PDF] [PubMed]

Commentary Cardiovascular and metabolic responses to catecholamine and sepsis prognosis: a ubiquitous phenomenon?
Collin S, Sennoun N, Levy BCritical Care, 2008 12:118 ( 17 March 2008 )
[Abstract] [Full text] [PDF] [PubMed]

Research Early acute kidney injury and sepsis: a multicentre evaluation
Bagshaw S, George C, Bellomo RCritical Care, 2008 12:R47 ( 10 April 2008 )
[Abstract] [Provisional PDF]

Research Introduction of medical emergency teams in Australia and New Zealand: a multi-centre study
Jones D, George C, Bellomo R, Hart G, Martin JCritical Care, 2008 12:R46 ( 7 April 2008 )
[Abstract] [Provisional PDF] [PubMed]


Research Risk factors for the development of nosocomial pneumonia and mortality on intensive care units: application of competing risks models
Wolkewitz M, Vonberg R, Grundmann H, Beyersmann J, Gastmeier P, Baerwolff S, Geffers C, Behnke M, Rueden H, Schumacher MCritical Care, 2008 12:R44 ( 2 April 2008 )
[Abstract] [Provisional PDF] [PubMed]

Letter Saccharomyces boulardii fungaemia in an intensive care unit patient treated with caspofungin
Nikolaos L, Dimitrios V, Hellen M, Sofia K, Aristea V, Charis T, Chronis T, Angellos P, Ioannis PCritical Care, 2008 12:414 ( 9 April 2008 ) [Abstract] [Full text] [PDF]

Letter Prehospital therapeutic hypothermia in cardiac arrest: will there ever be evidence? Schefold J, Storm C, Hasper DCritical Care, 2008 12:413 ( 9 April 2008 ) [PDF]

Letter Discriminating invasive fungal infection from colonization
Blot S, Vandewoude K, Vogelaers DCritical Care, 2008 12:412 ( 3 April 2008 ) [PDF]

BMJ Table of Contents: 12 April

Continuous deep sedation in patients nearing death
Scott A Murray, Kirsty Boyd, and Ira Byock

Cardiopulmonary resuscitation for out of hospital cardiac arrest
Jasmeet Soar and Jerry P Nolan

Oral bisphosphonates and atrial fibrillation
Sumit R Majumdar

Selecting medical students
Celia A Brown and Richard J Lilford

BioMed Central: Influence of airway management strategy ...

Research article Influence of airway management strategy on No-Flow-Time during an Advanced Life Support Course for intensive care nurses - a single rescuer resuscitation manikin study Wiese C, Bartels U, Schultens A, Steffen T, Torney A, Bahr J, Graf
BBMC Emergency Medicine, 2008 8:4 ( 10 April 2008 )
[Abstract] [Provisional PDF]