Maximum Norepinephrine Dosage Within 24 Hours as an Indicator of Refractory Septic Shock: A Retrospective Study

Abstract

Background: The management of refractory septic shock remains a major challenge in critical care and its early indicators are not fully understood. We hypothesized that the maximum norepinephrine dosage within 24 hours of intensive care unit (ICU) admission may be a useful indicator of early mortality in patients with septic shock. Methods: In this retrospective single-center observational study, patients with septic shock admitted to the emergency ICU of an academic medical center between April 2011 and March 2017 were included. Individuals with cardiac arrest and those with do-not-resuscitate orders before admission were excluded. We analyzed if the maximum norepinephrine dosage within 24 hours of ICU admission (MD24) was associated with 7-day mortality. Results: Among 152 patients with septic shock, 20 (15%) did not survive by day 7. The receiver operating characteristic curve analysis for predicting 7-day mortality revealed a cutoff of MD24 of 0.6 μg/kg/min (sensitivity 47%, specificity 93%). In the multivariable regression analysis, a higher MD24 was significantly associated with 7-day mortality (odds ratio: 7.20; 95% confidence interval [CI]: 2.02-25.7; P = .002) but not with 30-day mortality. Using the inverse probability of treatment weighting method in a propensity scoring analysis, a higher MD24 was significantly associated with 7-day (hazard ratio [HR]: 8.9; 95% CI: 3.2-25.0; P < .001) and 30-day mortality (HR: 2.7; 95% CI: 1.2-5.8; P = .012). Conclusions: An MD24 ≥0.6 μg/kg/min was significantly associated with 7-day mortality in patients with septic shock and may therefore be a useful indicator of refractory septic shock.

Correlation and Prognostic Assessment of Low T3 Syndrome and Norepinephrine Dosage for Patients with Sepsis: A Retrospective Single-Center (Cohort) Study

“…Furthermore, the ROC curve and multivariate Cox regression model analyses confirmed that the MDN was an efficient prognostic indicator for mortality in patients with septic shock. This conclusion was in line with the results of a previous study that evaluated 7-day mortality, 11 which was different from the 28-day mortality used in the current study. Combining the results of the previous study and this current study, 11 it can be concluded that the dosage of norepinephrine is a prognostic indicator of both early and late mortality and should be paid close attention to.…”

“…This conclusion was in line with the results of a previous study that evaluated 7-day mortality, 11 which was different from the 28-day mortality used in the current study. Combining the results of the previous study and this current study, 11 it can be concluded that the dosage of norepinephrine is a prognostic indicator of both early and late mortality and should be paid close attention to. Furthermore, another study demonstrated that there was no difference in the 28-day mortality by performing a subgroup analysis with a norepinephrine dosage cut-off of 0.04 µg/kg/min.…”

“…The following clinical data were obtained from the electronic medical records of the included patients: infection diagnosis, initial vital signs (heart rate [HR], respiratory rate [RR], MAP, and body temperature) at the time of ICU admission, indicators within the first 24 h (thyroid hormone levels [TSH, FT3, FT4], SOFA score, 15 procalcitonin [PCT], and fluid resuscitation volume), lactic acid levels at the time of ICU admission and the second 24 h, the maximum dosage of norepinephrine (MDN) within 72 h in patients with septic shock, microbiological results and adjunctive treatment (erythrocyte infusion 3 days before admission and 3 days after admission, noninvasive mechanical ventilation [NMV], duration of invasive mechanical ventilation [IMV], and continuous renal replace treatment [CRRT]). Referring to the methods of previous studies, 11 , 16 the MDN within 72 h was calculated by dividing the total dosage in 72 h by the actual body weight and the number of minutes of norepinephrine use.…”

“… 10 On the contrary, another study showed that a maximum dosage of norepinephrine, which was ≥ 0.6 µg/kg/min, was notably associated with 7-day mortality in patients with septic shock. 11 Although the duration of mortality studied was different between the two reports, the correlation between the norepinephrine dosage and prognosis in patients with septic shock remains unclear.…”

“…Secondly, among the 169 patients, 138 patients were allocated to the low T3 group, accounting for 81.7%, which is the inherent selection bias of the retrospective study. Thirdly, in this study, the MDN was calculated regarding the methods of literature, 11 , 16 but other vasopressors dosages were not converted to the norepinephrine equivalent dosage, which was one of the limitations of this study and needs to be applied in future studies. Consequently, since this study is a retrospective study, further, larger prospective studies with more study participants are required to explore the correlation between LTS and norepinephrine dosage.…”