Delayed vasopressor initiation is associated with increased mortality in patients with septic shock

Hidalgo, Daniel Colon; Patel, Jaimini; Masic, Dalila; Park, David; Rech, Megan A.

doi:10.1016/j.jcrc.2019.11.004

Cited by 64 publications

(50 citation statements)

References 18 publications

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“…It is interesting to note that the norepinephrine dosing is similar between actual and optimal strategy on day 1, which supports the well-accepted concept that adequate fluid infusion should be given before considering vasopressors. Results from observational studies showed that early norepinephrine use is associated with improved mortality outcome [ 51 – 54 ], which is further supported by a small RCT [ 55 ]. This is not contradictory to our results.…”

Section: Discussionmentioning

confidence: 87%

Individualized resuscitation strategy for septic shock formalized by finite mixture modeling and dynamic treatment regimen

Ma¹,

Liu

Shen

et al. 2021

Crit Care

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Background Septic shock comprises a heterogeneous population, and individualized resuscitation strategy is of vital importance. The study aimed to identify subclasses of septic shock with non-supervised learning algorithms, so as to tailor resuscitation strategy for each class. Methods Patients with septic shock in 25 tertiary care teaching hospitals in China from January 2016 to December 2017 were enrolled in the study. Clinical and laboratory variables were collected on days 0, 1, 2, 3 and 7 after ICU admission. Subclasses of septic shock were identified by both finite mixture modeling and K-means clustering. Individualized fluid volume and norepinephrine dose were estimated using dynamic treatment regime (DTR) model to optimize the final mortality outcome. DTR models were validated in the eICU Collaborative Research Database (eICU-CRD) dataset. Results A total of 1437 patients with a mortality rate of 29% were included for analysis. The finite mixture modeling and K-means clustering robustly identified five classes of septic shock. Class 1 (baseline class) accounted for the majority of patients over all days; class 2 (critical class) had the highest severity of illness; class 3 (renal dysfunction) was characterized by renal dysfunction; class 4 (respiratory failure class) was characterized by respiratory failure; and class 5 (mild class) was characterized by the lowest mortality rate (21%). The optimal fluid infusion followed the resuscitation/de-resuscitation phases with initial large volume infusion and late restricted volume infusion. While class 1 transitioned to de-resuscitation phase on day 3, class 3 transitioned on day 1. Classes 1 and 3 might benefit from early use of norepinephrine, and class 2 can benefit from delayed use of norepinephrine while waiting for adequate fluid infusion. Conclusions Septic shock comprises a heterogeneous population that can be robustly classified into five phenotypes. These classes can be easily identified with routine clinical variables and can help to tailor resuscitation strategy in the context of precise medicine.

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Section: Discussionmentioning

confidence: 87%

Individualized resuscitation strategy for septic shock formalized by finite mixture modeling and dynamic treatment regimen

Ma¹,

Liu

Shen

et al. 2021

Crit Care

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“…2017 Single center, RCT 310 155 155 Elbouhy et al [ 30 ] 2019 Egypt Jan. 2017–Dec. 2018 Single center, RCT 101 57 44 Colon Hidalgo et al [ 25 ] 2020 USA Jan. 2017–Jul. 2017 Single center, retrospective cohort study 119 76 43 Ospina-Tascón et al [ 26 ] 2020 Colombia Jan. 2015–Feb.…”

Section: Resultsmentioning

confidence: 99%

“…Colon Hidalgo et al 2020 [25] The time when vasopressors were initiated ≤ 6 h The time when vasopressors were initiated > 6 h…”

Section: Discussionmentioning

confidence: 99%

Timing of norepinephrine initiation in patients with septic shock: a systematic review and meta-analysis

Zhang

2020

Crit Care

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Background The effect of the timing of norepinephrine initiation on clinical outcomes in patients with septic shock is uncertain. A systematic review and meta-analysis was performed to evaluate the impact of early and late start of norepinephrine support on clinical outcomes in patients with septic shock. Methods We searched the PubMed, Cochrane, and Embase databases for randomized controlled trials (RCTs) and cohort studies from inception to the 1st of March 2020. We included studies involving adult patients (> 18 years) with septic shock. All authors reported our primary outcome of short-term mortality and clearly comparing early versus late norepinephrine initiation with clinically relevant secondary outcomes (ICU length of stay, time to achieved target mean arterial pressure (≥ 65 mmHg), and volume of intravenous fluids within 6 h). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI). Results Five studies including 929 patients were included. The primary outcome of this meta-analysis showed that the short-term mortality of the early group was lower than that of the late group (odds ratio [OR] = 0.45; 95% CI, 0.34 to 0.61; P < 0.00001; χ 2 = 3.74; I 2 = 0%). Secondary outcomes demonstrated that the time to achieved target MAP of the early group was shorter than that of the late group (mean difference = − 1.39; 95% CI, − 1.81 to − 0.96; P < 0.00001; χ 2 = 1.03; I 2 = 0%). The volume of intravenous fluids within 6 h of the early group was less than that of the late group (mean difference = − 0.50; 95% CI, − 0.68 to − 0.32; P < 0.00001; χ 2 = 33.76; I 2 = 94%). There was no statistically significant difference in the ICU length of stay between the two groups (mean difference = − 0.11; 95% CI, − 1.27 to 1.05; P = 0.86; χ 2 = 0.85; I 2 = 0%). Conclusions Early initiation of norepinephrine in patients with septic shock was associated with decreased short-term mortality, shorter time to achieved target MAP, and less volume of intravenous fluids within 6 h. There was no significant difference in ICU length of stay between early and late groups. Further large-scale RCTs are still required to confirm these results.

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“…Different studies have evaluated the effects of early NE administration in septic shock patients. Two retrospective studies by Colon-Hidalgo [ 43 ] and Bai [ 44 ] have shown that the time to NE initiation is an independent predictor of mortality. In this regard the CENSER trial has directly compared early NE administration to NE administration only when fluid therapy has failed [ 45 ].…”

Section: Vasopressorsmentioning

confidence: 99%

Management of sepsis and septic shock in the emergency department

2021

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Early management of sepsis and septic shock is crucial for patients’ prognosis. As the Emergency Department (ED) is the place where the first medical contact for septic patients is likely to occur, emergency physicians play an essential role in the early phases of patient management, which consists of accurate initial diagnosis, resuscitation, and early antibiotic treatment. Since the issuing of the Surviving Sepsis Campaign guidelines in 2016, several studies have been published on different aspects of sepsis management, adding a substantial amount of new information on the pathophysiology and treatment of sepsis and septic shock. In light of this emerging evidence, the present narrative review provides a comprehensive account of the recent advances in septic patient management in the ED.

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Delayed vasopressor initiation is associated with increased mortality in patients with septic shock

Cited by 64 publications

References 18 publications

Individualized resuscitation strategy for septic shock formalized by finite mixture modeling and dynamic treatment regimen

Individualized resuscitation strategy for septic shock formalized by finite mixture modeling and dynamic treatment regimen

Timing of norepinephrine initiation in patients with septic shock: a systematic review and meta-analysis

Management of sepsis and septic shock in the emergency department

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