Duration Of Vasopressor Therapy Research Articles

Restrictive resuscitation in patients with sepsis and mortality: A systematic review and meta-analysis with trial sequential analysis.

Although fluid resuscitation is recommended by the Society of Critical Care Medicine Surviving Sepsis Campaign Guidelines, risks of volume overload persist.The objective of this systematic review is to assess the effects of a restrictive fluid resuscitation approach in the septic patient both during and after the initial resuscitation period (30 ml/kg). A systematic review and meta-analysis with trial sequential analysis (TSA) of randomized controlled trials was conducted. Two blinded reviewers independently assessed and included studies that evaluated adult patients with sepsis involving a comparator group with an effective restrictive fluid resuscitation approach. The primary outcome was mortality. Secondary outcomes included rates of acute kidney injury (AKI), renal replacement therapy (RRT), ventilator days, intensive care unit (ICU) and hospital length of stay (LOS), duration of vasopressor therapy, and limb (or digital) ischemia. PubMed and Medline databases were queried for the search. A total of eight trials in 2375 patients were included. Effective restrictive fluid resuscitation compared with standard of care. The risk of bias was high in six studies and low in two studies, and all studies implemented fluid restriction after a 30-ml/kg infusion of fluids. Fluid restriction did not significantly reduce mortality in all studies compared to usual care (37% vs. 40% with usual care; risk ratio [RR] 0.90, 95% confidence interval [CI] 0.76-1.06, p=0.23, I2 =24%) or by TSA findings. There were no significant differences in rates of AKI or RRT (5 studies), LOS in ICU (4 studies) or hospital (3 studies), duration of vasopressor therapy (6 studies), or incidence of limb or digital ischemia (3 studies). However, fluid restriction significantly reduced ventilator days as evaluated in seven studies (mean difference - 1.25 days, 95% CI -1.92 to -0.58 days, p=0.0003, I2 =90%). This study demonstrated that a restrictive resuscitation strategy in sepsis resulted in no difference in mortality but may reduce ventilator days. Larger randomized trials are required to determine the optimal management of fluids in patients with sepsis.

63: RESTRICTIVE FLUIDS IN SEPSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Introduction: While large-volume fluid resuscitation as a part of early-goal directed therapy (EGDT) for sepsis has been widely adopted and endorsed by the SCCM Surviving Sepsis Guidelines, the risks of volume overload in the critically ill challenge this approach. The objective of this study is to assess the effects of a restrictive fluid resuscitation approach in sepsis given divergent results from randomized studies. Methods: A systematic review using a random effects meta-analysis with trial sequential analysis (TSA) of randomized controlled trials published from 2001 were evaluated. Studies were included if they evaluated adult patients with sepsis or septic shock involving a comparator group with an effective restrictive resuscitation approach. Two blinded reviewers independently assessed studies for inclusion and risk of bias and extracted data using Cochrane Collaborative methodology. The primary outcome was the incidence of mortality at the latest reported study period. Secondary outcomes included rates of acute kidney injury (AKI), ventilator days, intensive care unit (ICU) and hospital length of stay (LOS), duration of vasopressor therapy, and limb ischemia. Results: A total of 2,375 patients were included among the 8 trials analyzed. The risk of bias was high in 6 studies and low in 2 studies. All studies implemented fluid restriction after an initial 30 mL/kg volume. Use of a restrictive resuscitation approach did not significantly reduce mortality in all studies compared to usual care (37% vs 40% with usual care; risk ratio [RR] 0.94, 95% confidence interval [CI] 0.85–1.04, P=0.25, I2 = 24%) and was confirmed by TSA findings. There were no significant differences in rates of AKI (5 studies), LOS in ICU (4 studies) or hospital (2 studies), duration of vasopressor therapy (6 studies), or incidence of limb ischemia (3 studies). However, a restrictive resuscitation strategy significantly reduced ventilator days evaluated in 7 studies (mean difference -1.25 days, 95% CI -0.59 to -1.93 days, P=0.0003, I2 = 90%). Conclusions: This meta-analysis demonstrated that a restrictive fluid resuscitation strategy in sepsis resulted in no difference in mortality but may reduce ventilator days. Larger randomized trials are required to determine the optimal management of fluids in patients with sepsis.

Efficacy of High-Dose Vitamin C Infusion on Outcomes in Sepsis Requiring Mechanical Ventilation: A Double-Blind Randomized Controlled Trial.

Background Critically ill patients have an increased requirement for vitamin C in sepsis and these patients have low levels of vitamin C. The researchers validated the efficacy of high-dose vitamin C intravenous infusion (IVI) in patients with sepsis requiring mechanical ventilation. Methods Forty patients were randomly assigned to 2 groups (20 each) in a 1 : 1 ratio in accordance with the vitamin C treatment regimen: Group I (GI): patients received 1.5 g/6 h vitamin C in 50 ml of dextrose 5% in water (D5W) IVI over 30 minutes for 4 consecutive days; Group II (GII): patients received 100 mg vitamin C/day as a first single dose in 50 ml of D5W IVI over 30 minutes and the other three subsequent doses were 50 ml of plain D5W IVI over 30 minutes for 4 consecutive days. Primary outcomes were the change in sequential organ failure assessment (SOFA) score at day 7, the incidence of ventilator-associated pneumonia (VAP), and the plasma vitamin C level. The glutathione peroxidase (GPX) activity, C-reactive protein (CRP) level, duration of vasopressor therapy, and 28-day mortality were secondary outcomes. Results The change in SOFA score at day 7 showed a significant difference between GI and GII (p < 0.001). The incidence of early VAP was significantly lower in GI (p=0.044). Vitamin C levels showed a significant rise in GI at day 1 and day 4 (p < 0.001 and p < 0.001, respectively). GPX activity of day 4 and day 7 was significantly higher in GI (p=0.005 and p=0.014, respectively). CRP levels of day 4 and day 7 were significantly higher in GII (p < 0.001 and p < 0.001, respectively). There was a significant difference in 28-day mortality (p=0.038) and duration of vasopressor therapy (p=0.033) in GI compared to GII. Conclusion The early use of high-dose vitamin C intravenous infusion in patients with sepsis requiring mechanical ventilation in combination with the standard treatment for sepsis lowered the incidence of VAP, increased the antioxidant status, and improved the illness severity. Trial Registration. This trial is registered with ClinicalTrials.gov Identifier (NCT04029675).

Unanswered questions on the use of hydrocortisone, ascorbic acid, and thiamine therapy in sepsis and septic shock.

To evaluate current evidence on the utility of hydrocortisone, ascorbic acid, and thiamine (HAT) therapy for the management of septic shock. The following keyword search terms were utilized in PubMed to identify relevant articles: ascorbic acid, thiamine, hydrocortisone, shock, and critical care. Articles relevant to HAT therapy in patients with septic shock were selected. Retrospective cohorts and randomized controlled trials were included in this review; case reports/series were excluded. Data from included studies illustrating the use of HAT therapy for the management of sepsis and septic shock, including data on time to HAT therapy initiation, severity of illness at baseline, duration of vasopressor therapy, progression of organ failure, and mortality, were evaluated. The utilization of HAT therapy for the management of sepsis and septic shock remains controversial. Hemodynamic benefits have been shown to be most pronounced when HAT therapy is initiated earlier. Future studies directed at earlier initiation may be necessary to confirm this theory.

Vasopressor-Sparing Strategies in Patients with Shock: A Scoping-Review and an Evidence-Based Strategy Proposition.

Despite the abundant literature on vasopressor therapy, few studies have focused on vasopressor-sparing strategies in patients with shock. We performed a scoping-review of the published studies evaluating vasopressor-sparing strategies by analyzing the results from randomized controlled trials conducted in patients with shock, with a focus on vasopressor doses and/or duration reduction. We analyzed 143 studies, mainly performed in septic shock. Our analysis demonstrated that several pharmacological and non-pharmacological strategies are associated with a decrease in the duration of vasopressor therapy. These strategies are as follows: implementing a weaning strategy, vasopressin use, systemic glucocorticoid administration, beta-blockers, and normothermia. On the contrary, early goal directed therapies, including fluid therapy, oral vasopressors, vitamin C, and renal replacement therapy, are not associated with an increase in vasopressor-free days. Based on these results, we proposed an evidence-based vasopressor management strategy.

The impact of selenium administration on severe sepsis or septic shock: a meta-analysis of randomized controlled trials.

The efficacy of selenium administration to treat severe sepsis or septic shock remains controversial. We conduct a systematic review and meta-analysis to explore the impact of selenium administration on severe sepsis or septic shock. We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through May 2020 for randomized controlled trials (RCTs) assessing the effect of selenium administration on severe sepsis or septic shock. Meta-analysis is performed using the random-effect model. Five RCTs involving 1482 patients are included in the meta-analysis. Overall, compared with control group in septic patients, selenium administration is not associated with reduced 28-day mortality (RR=0.93; 95% CI=0.73 to 1.19; P=0.58), but results in substantially decreased all-cause mortality (RR=0.78; 95% CI=0.63 to 0.98; P=0.03) and length of hospital stay (MD=-3.09; 95% CI=-5.68 to -0.50; P=0.02). Selenium administration results in notable decrease in all-cause mortality and length of hospital stay, but shows no substantial influence on the 28-day mortality, length of ICU stay, duration of vasopressor therapy, the incidence of acute renal failure, adverse events, and serious adverse events for septic patients.

Vasopressin in vasoplegic shock: A systematic review.

BACKGROUNDVasoplegic shock is a challenging complication of cardiac surgery and is often resistant to conventional therapies for shock. Norepinephrine and epinephrine are standards of care for vasoplegic shock, but vasopressin has increasingly been used as a primary pressor in vasoplegic shock because of its unique pharmacology and lack of inotropic activity. It remains unclear whether vasopressin has distinct benefits over standard of care for patients with vasoplegic shock. AIMTo summarize the available literature evaluating vasopressin vs non-vasopressin alternatives on the clinical and patient-centered outcomes of vasoplegic shock in adult intensive care unit (ICU) patients.METHODSThis was a systematic review of vasopressin in adults (≥ 18 years) with vasoplegic shock after cardiac surgery. Randomized controlled trials, prospective cohorts, and retrospective cohorts comparing vasopressin to norepinephrine, epinephrine, methylene blue, hydroxocobalamin, or other pressors were included. The primary outcomes of interest were 30-d mortality, atrial/ventricular arrhythmias, stroke, ICU length of stay, duration of vasopressor therapy, incidence of acute kidney injury stage II-III, and mechanical ventilation for greater than 48 h.RESULTSA total of 1161 studies were screened for inclusion with 3 meeting inclusion criteria with a total of 708 patients. Two studies were randomized controlled trials and one was a retrospective cohort study. Primary outcomes of 30-d mortality, stroke, ventricular arrhythmias, and duration of mechanical ventilation were similar between groups. Conflicting results were observed for acute kidney injury stage II-III, atrial arrhythmias, duration of vasopressors, and ICU length of stay with higher certainty of evidence in favor of vasopressin serving a protective role for these outcomes.CONCLUSIONVasopressin was not found to be superior to alternative pressor therapy for any of the included outcomes. Results are limited by mixed methodologies, small overall sample size, and heterogenous populations.

Vasopressin in Conjunction With Norepinephrine in Septic Shock: A Retrospective Cohort Study From a Low Middle-Income Country.

Objectives:Guidelines recommend use of norepinephrine as the first-line treatment for fluid-refractory septic shock and if septic shock persists vasopressin may be initiated. Since there are limited data from low middle-income countries with high disease burden of sepsis, we aimed to compare the outcomes of using vasopressin adjunct to norepinephrine in comparison with norepinephrine alone.Design:Retrospective cohort study.Setting:Aga Khan University Hospital, Karachi, Pakistan.Patients:Six-hundred fifty-three patients diagnosed with septic shock from January 2019 to December 2019, with 498 given norepinephrine only and 155 given norepinephrine-vasopressin combination.Interventions:None.Measurements and Main Results:Primary outcome was in-hospital mortality. Secondary outcomes were duration of vasopressor used, length of hospital stay, length of ICU stay, and days on ventilatory support. After adjustment by multivariable logistic regression, it was found that mortality was not significantly associated with the norepinephrine-vasopressin combination (adjusted odds ratio, 0.633 [95% CI, 0.370–1.081]). However, Sequential Organ Failure Assessment score at admission (1.100 [1.014–1.193]), lactate at admission (1.167 [1.109–1.227]), duration of vasopressor used (1.481 [1.316–1.666]), and level of care (3.025 [1.682–5.441]) were found to be independently associated with the adjunct usage of norepinephrine and vasopressin.Conclusions:The use of norepinephrine-vasopressin combination has remained debatable in literature. Our study showed that although there was no difference in mortality between the two groups, admission Sequential Organ Failure Assessment scores and admission lactate levels were found to be significantly higher in the norepinephrine-vasopressin group. Hence, physicians from Pakistan used the norepinephrine-vasopressin combination in resistant septic shock patients who were sicker to begin with. Furthermore, duration of vasopressor therapy and ICU admission were also significantly higher in the combination group. Considering the recent hyperinflation of vasopressors costs and that most healthcare expenditure for patients in Pakistan is out-of-pocket, this can consequently lead to unwarranted financial burden for patients and their families.

Vasopressor Use for Severe Hypotension-A Multicentre Prospective Observational Study.

BackgroundThe optimal approach to titrate vasopressor therapy is unclear. Recent sepsis guidelines recommend a mean arterial pressure (MAP) target of 65 mmHg and higher for chronic hypertensive patients. As data emerge from clinical trials comparing blood pressure targets for vasopressor therapy, an accurate description of usual care is required to interpret study results. Our aim was to measure MAP values during vasopressor therapy in Canadian intensive care units (ICUs) and to compare these with stated practices and guidelines.MethodIn a multicenter prospective cohort study of critically ill adults with severe hypotension, we recorded MAP and vasopressor doses hourly. We investigated variability across patients and centres using multivariable regression models and Analysis of variance (ANOVA), respectively.ResultsWe included data from 56 patients treated in 6 centers. The mean (standard deviation [SD]) age and Acute Physiology and Chronic Health Evaluation (APACHE) II score were 64 (14) and 25 (8). Half (28 of 56) of the patients were at least 65 years old, and half had chronic hypertension. The patient-averaged MAP while receiving vasopressors was 75 mm Hg (6) and the median (1st quartile, 3rd quartile) duration of vasopressor therapy was 43 hours (23, 84). MAP achieved was not associated with history of underlying hypertension (p = 0.46) but did vary by center (p<0.001).ConclusionsIn this multicenter, prospective observational study, the patient-level average MAP while receiving vasopressors for severe hypotension was 75 mmHg, approximately 10 mmHg above current recommendations and stated practices. Moreover, our results do not support the notion that clinicians tailor vasopressor therapy to individual patient characteristics such as underlying chronic hypertension but MAP achieved while receiving vasopressors varied by site.

The Effect of High-dose Parenteral Sodium Selenite in Critically Ill Patients following Sepsis: A Clinical and Mechanistic Study.

Introduction:Severe sepsis and septic shock is characterized by inflammation and oxidative stress. Selenium levels have been reported to be low due to loss or increased requirements during severe sepsis and septic shock. We investigated the effect of high-dose parenteral selenium administration in septic patients.Methods:A prospective, randomized control clinical trial was performed in septic patients. After randomization, patients in selenium group received high-dose parenteral sodium selenite (2 mg intravenous [IV] bolus followed by 1.5 mg IV continuous infusion daily for 14 days) plus standard therapy and the control group received standard therapy. The primary endpoint was mortality at 28 days. Changes in the mean levels of high mobility group box-1 (HMGB-1) protein and superoxide dismutase (SOD), duration of vasopressor therapy, incidence of acute renal failure, and 60 days’ mortality were secondary endpoints.Results:Fifty-four patients were randomized into selenium group (n = 29) and control group (n = 25). There was no significant difference in 28-day mortality. No significant difference between the two groups with respect to the average levels of HMGB-1 protein and SOD at any point in time over the course of 14 days had observed.Conclusion:In early administration within the first 6 h of sepsis diagnosis, our study demonstrated that high-dose parenteral selenium administration had no significant effect either on 28-day mortality or the mean levels of HMGB-1 and SOD (Trial Registration: IRCT201212082887N4 at WHO Clinical Trial Registry, August 29, 2014).

Continuation of Statin Therapy and Vasopressor Use in Septic Shock.

Studies have evaluated the use of statins in sepsis; however, no human studies have explored their effect on vasopressor requirements in septic shock. The primary objective was to determine the effect of prehospital statin continuation on duration of vasopressor therapy in patients with septic shock. Secondary objectives included maximum and average vasopressor dose and in-hospital mortality. This was a retrospective, institutional board-approved, observational cohort study in a community teaching hospital; 119 adult intensive care unit (ICU) patients with an ICD-9 code for septic shock and prehospital statin therapy were evaluated. Multivariate analyses were performed to address confounders. Of the 1229 patients screened, 119 (10%) met inclusion criteria; 73 patients (61%) had a statin continued within 24 hours of ICU admission. Crude analysis demonstrated no difference in vasopressor duration in the statin versus no statin group (3.3 vs 4.8 days; P = 0.21). There was no difference in either maximum (17.9 ± 16.1 vs 23.8 ± 21.7 µg/min norepinephrine equivalents [NEQs]; P = 0.1) or average vasopressor dose (9.5 ± 8.4 vs 12.1 ± 11.5 µg/min NEQ; P = 0.17). There was a decrease in mortality in the statin patients (43% vs 67 %; P = 0.05). On adjustment for potential confounders, there was no difference in any outcome, with a persistent trend toward lower mortality in the statin group. Continuation of prehospital statin therapy decreased neither duration nor dose of vasopressors in patients with septic shock but yielded a trend toward decreased mortality.

Temporizing surgical management improves outcome in patients with Vibrio necrotizing fasciitis complicated with septic shock on admission

BackgroundNecrotizing fasciitis (NF) caused by Vibrio infection is one of the most fatal diseases, resulting in high morbidity and mortality. Early diagnosis and effective surgical intervention are the mainstays for better outcomes for affected patients. Currently, standard surgical management calls for prompt and aggressive debridement and amputation. However, due to its rapid progression and deterioration, 50–60% of Vibrio NF cases present with septic shock and multiple organ dysfunction on admission. These patients, who usually have many surgical contraindications, are unable to tolerate a prolonged aggressive surgical debridement. Therefore, determining the optimal surgical intervention for these particularly severe patients remains a formidable problem in emergency medicine. MethodsA retrospective study was conducted on patients who underwent surgery for Vibrio NF and septic shock on admission to the emergency room from April 2001 to October 2012. These patients received the same treatment protocol, with the exception of the initial surgical intervention strategy. Nineteen patients were treated with a temporizing strategy, which called for simple incisions and drainage under regional anesthesia, followed by complete debridement 24h later. Another fifteen patients underwent aggressive surgical debridement during the first operative procedure. Basic demographics, laboratory results on admission, clinical course and outcomes were compared to assess the efficacy and safety of two initial surgical treatment methods: the temporizing strategy and the aggressive strategy. ResultsThirty-four patients were included in this study, and the average age was 51.65 years. Chronic liver disease was the most prevalent preexisting condition (50.00%) and the lower limbs were most commonly involved in infection (76.47%). In this patient population, 19 cases underwent surgery with a temporizing therapeutic strategy, while the remaining 15 cases were treated with an aggressive surgical strategy. There were no differences between the two groups with respect to demographics, severity of illness and laboratory data. Compared with those treated with the aggressive strategy, patients treated with the temporizing strategy had shorter operation time (40.79±16.61 vs. 102.00±18.97min, p<0.001), less bleeding (120.53±67.20 vs. 417.33±134.72mL, p<0.001), a reduced amount of intraoperatively administrated fluid (3144.70±554.71 vs. 1637.40±302.11mL, p<0.001), decreased maximum dose of dopamine (15.73±5.64 vs. 10.47±5.61μg/kg/min, p=0.011) and noradrenaline (20.13±7.50 vs. 13.37±6.18μg/kg/min, p=0.007), lower arterial lactate values at the end of surgery (5.56±1.99 vs. 8.66±3.25mmol/L, p=0.004), and, most importantly, lower mortality (26.32% vs. 60.00%, p=0.048). All other treatment conditions, such as duration of vasopressor therapy, number of debridement procedures, rate of amputation, ICU length of stay and hospital length of stay, were the same for both groups. ConclusionThe temporizing strategy, with early initiation of simple incisions and drainage under regional anesthesia followed by complete debridement 24h later, is more feasible and effective for patients with Vibrio NF complicated with septic shock, as compared with the aggressive surgical debridement strategy.

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Introduction: Ethnic differences in adrenergic receptor density and sensitivity has been suggested to play a key role in the response to antihypertensive cardiovascular drug therapy. The impact of ethnicity for the critically ill patient requiring cardiovascular drug support has not been described. Currently in the intensive care unit (ICU), ethnicity is not considered in the management of vasopressor (VP) therapy of septic shock patients. Hypothesis: VP requirements for septic shock patients in the ICU vary between two ethnic groups: African Americans (AA) and Caucasians (CA). Methods: A retrospective cohort study conducted in an urban, academic tertiary care center. Septic shock patients admitted from October 2008 to December 2010 were evaluated. Baseline demographics included age, gender, co-morbidities, source of infection, and APACHE II scores. VP dosing, duration, and mean (using hourly dose) were collected. Univariate analysis with Chi-square, Fisher’s exact test or t-test was performed. Results: 90 of 203 patients evaluated with septic shock requiring VP support initiated in the ICU were included. 54 (60%) patients were AA and 36 (40%) were CA. There were no significant differences in baseline demographics, except end stage renal disease in AA (P=0.001). The mean APACHE II score was 19.5 ± 5.8 for AA and 19.4 ± 7.7 for CA (P=0.9). Norepinephrine was used in 89%, vasopressin 37%, phenylephrine 27%, dopamine 8% and epinephrine 4% of patients. 59% of the patients required one VP, 24% required two VP and 17% required? 3 VP. There were no statistical differences in time to goal mean arterial pressure, fluid requirements or duration of VP therapy between AA and CA.For phenylephrine, higher starting (72.7 mcg/min vs. 25.5 mcg/min, P=0.03), maximum (238.7 mcg vs. 149.5 mcg, P=0.04), and mean (171.1 mcg vs. 90.4 mcg, P=0.02) doses were required in AA compared to CA, respectively. For norepinephrine, AA required a higher mean dose (23.4 mcg/min vs. 13.6 mcg/min, P=0.03) compared to CA. Conclusions: A significant ethnic-based variation in the requirements of phenylephrine and norepinephrine was found between AA and CA septic shock patients with no significant difference in vasopressor duration or fluid requirements.

REPLY

Reply: The authors thank Dr Myrianthefs et al. for the interest in our recently published article on γ-globulin levels in patients with community-acquired septic shock (1). These authors reported a lower incidence (32% vs. 57%) of low immunoglobulin G (IgG) levels in a cohort of 38 patients than we did in our study population. In addition, they did not find any difference in the duration of vasopressor therapy or mechanical ventilation between the two populations. These discrepancies could be explained by the different populations. First, they studied intensive care unit (ICU)-acquired infections, whereas we studied community-acquired infections. Second, we excluded patients with monoclonal production of IgG (4 of 29 patients screened) or with hematologic diseases. It is quite possible that in a hospital population with multiple comrplications and pre-existing diseases, some patients could have monoclonal production of IgG and, thus, be, perhaps wrongly, considered as having normal IgG levels. We can expect that IgG levels will eventually return to the reference ranges some time after the onset of the septic shock. We did not document this because the ICU stay was quite short (median, 6 days) and we did not check immunoglobulin levels after ICU discharge. In contrast, the median ICU stay in the study from Myrianthefs et al. was more than 30 days. Mortality in the study by Myrianthefs et al. was much higher than that in our study (42% vs. 29%). Interestingly, the combined mortality for the two studies was 9 (26%) of 35 in the "normal IgG" level group compared with 13 (54%) of 24 in the "low IgG" level group (P = 0.03), with a relative risk of death of 2.11 (1.07 - 4.13) and an odds ratio of 3.41 (1.13 - 10.30). This supports our conclusion that patients with septic shock and low IgG levels have a higher mortality rate than patients with normal IgG levels, and that this population could be a target for the administration of i.v. immunoglobulins. NB: Table 1: The mortality in the "normal IgG" level group is 9 of 26, i.e., 34%, and not 26.9%. We could not confirm the P value presented by the authors (P = 0.29 using the Fisher exact test and P = 0.17 using the chi-square test). We suppose that there was an error in the Table. Fabio Silvio Taccone Daniel De Backer Jean-Louis Vincent Erasme Hospital Université Libre de Bruxelles Bruxelles, Belgium