Evaluation of Vasopressor Exposure and Mortality in Patients With Septic Shock.

OBJECTIVES: The objectives of this study were to: 1) determine the association between vasopressor dosing intensity during the first 6 hours and first 24 hours after the onset of septic shock and 30-day in-hospital mortality; 2) determine whether the effect of vasopressor dosing intensity varies by fluid resuscitation volume; and 3) determine whether the effect of vasopressor dosing intensity varies by dosing titration pattern. DESIGN: Multicenter prospective cohort study between September 2017 and February 2018. Vasopressor dosing intensity was defined as the total vasopressor dose infused across all vasopressors in norepinephrine equivalents. SETTING: Thirty-three hospital sites in the United States (n = 32) and Jordan (n = 1). PATIENTS: Consecutive adults requiring admission to the ICU with septic shock treated with greater than or equal to 1 vasopressor within 24 hours of shock onset. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Out of 1,639 patients screened, 616 were included. Norepinephrine (93%) was the most common vasopressor. Patients received a median of 3,400 mL (interquartile range, 1,851-5,338 mL) during the 24 hours after shock diagnosis. The median vasopressor dosing intensity during the first 24 hours of shock onset was 8.5 µg/min norepinephrine equivalents (3.4-18.1 µg/min norepinephrine equivalents). In the first 6 hours, increasing vasopressor dosing intensity was associated with increased odds ratio of 30-day in-hospital mortality, with the strength of association dependent on concomitant fluid administration. Over the entire 24 hour period, every 10 µg/min increase in vasopressor dosing intensity was associated with an increased risk of 30-day mortality (adjusted odds ratio, 1.33; 95% CI, 1.16-1.53), and this association did not vary with the amount of fluid administration. Compared to an early high/late low vasopressor dosing strategy, an early low/late high or sustained high vasopressor dosing strategy was associated with higher mortality. CONCLUSIONS: Increasing vasopressor dosing intensity during the first 24 hours after septic shock was associated with increased mortality. This association varied with the amount of early fluid administration and the timing of vasopressor titration.

Narrative Review of Controversies Involving Vasopressin Use in Septic Shock and Practical Considerations.

Objective: To summarize literature evaluating vasopressin use, focusing on clinical controversies regarding initiation, dosing, and discontinuation and interaction of vasopressin with other therapies in septic shock patients. Data Sources: A PubMed English-language literature search (January 2008 to December 2019) was performed using these terms: arginine vasopressin, septic, shock, and sepsis. Citations, including controlled trials, observational studies, review articles, guidelines, and consensus statements, were reviewed. Study Selection and Data Extraction: Relevant clinical data focusing on specific controversial questions regarding the utility of vasopressin in patients with septic shock were narratively summarized. Data Synthesis: Current literature does not strongly support the use of vasopressin as a first-line initial therapy for septic shock. Additionally, there are conflicting data for weight-based dosing of vasopressin in overweight patients. Evidence for vasopressin renal protection and interaction with corticosteroids is minimal. However, vasopressin has the ability to reduce catecholamine requirements in septic shock patients and may provide a mortality benefit in specific subgroups. Discontinuation of vasopressin last, not second to last, in resolving septic shock may reduce hypotension development. Relevance to Patient Care and Clinical Practice: This review addresses specific clinical controversies that drive vasopressin use in septic shock patients in real-world practice. Conclusion: Vasopressin should remain second-line adjunct to norepinephrine to augment mean arterial pressures. Dosing should be initiated at 0.03 U/min, and higher doses offer minimal benefit. There are conflicting data on the impact of weight on vasopressin response. Studies have failed to show renal benefit with vasopressin use or an interaction with corticosteroid therapy.

Balanced Crystalloids Versus Saline in Critically Ill Adults: A Systematic Review and Meta-analysis.

Background: The optimal resuscitative fluid remains controversial. Objective: To assess the association between crystalloid fluid and outcomes in critically ill adults. Methods: Cumulative Index to Nursing and Allied Health Literature, Scopus, PubMed, and Cochrane Central Register for Controlled Trials were searched from inception through July 2019. Cohort studies and randomized trials of critically ill adults provided predominantly nonperioperative fluid resuscitation with balanced crystalloids or 0.9% sodium chloride (saline) were included. Results: Thirteen studies (n = 30 950) were included. Balanced crystalloids demonstrated lower hospital or 28-/30-day mortality (risk ratio [RR] = 0.86; 95% CI = 0.75-0.99; I2 = 82%) overall, in observational studies (RR = 0.64; 95% CI = 0.41-0.99; I2 = 63%), and approached significance in randomized trials (RR = 0.94; 95% CI = 0.88-1.02; I2 = 0%). New acute kidney injury occurred less frequently with balanced crystalloids (RR = 0.91; 95% CI = 0.85-0.98; I2 = 0%), though progression to renal replacement therapy was similar (RR = 0.91; 95% CI = 0.79-1.04; I2 = 38%). In the sepsis cohort, odds of hospital or 28-/30-day mortality were similar, but the odds of major adverse kidney events occurring in the first 30 days were less with balanced crystalloids than saline (OR = 0.78; 95% CI = 0.66-0.91; I2 = 42%). Conclusion and Relevance: Resuscitation with balanced crystalloids demonstrated lower hospital or 28-/30-day mortality compared with saline in critically ill adults but not specifically those with sepsis. Balanced crystalloids should be provided preferentially to saline in most critically ill adult patients.

Effects From Continuous Infusions of Dexmedetomidine and Propofol on Hemodynamic Stability in Critically Ill Adult Patients With Septic Shock.

PURPOSE: To compare the development of clinically significant hemodynamic event (ie, hypotension or bradycardia) in adults with septic shock receiving either propofol or dexmedetomidine. MATERIALS AND METHODS: A retrospective cohort study of adults with septic shock admitted to an intensive care unit (ICU) at an academic medical center between July 2013 and July 2017. RESULTS: Patients in the propofol (n = 35) and dexmedetomidine (n = 37) groups developed a clinically significant hemodynamic event at similar frequencies (31.4 vs 29.7%, P = .99). All patients with an event experienced hypotension, whereas 2 (5.4%) patients in the dexmedetomidine group also experienced bradycardia. Most patients in both groups (70% vs 90%) received an escalating sedative dose, and almost half (42.9%) in the dexmedetomidine group had the sedative dosage increased more frequently than every 30 minutes. Patients in both groups had similar ICU (24.1 vs 24.3 days, P = .98) and hospital (37.9 vs 29.7 days, P = .29) lengths of stay. There was no difference in median time to hemodynamic event between the groups (propofol 1 hour [interquartile range, IQR: 0.5-9.9] vs dexmedetomidine 2 hours [IQR: 1.5-11.1 hours], P = .85). CONCLUSION: Patients with septic shock receiving propofol or dexmedetomidine experienced similar rates of clinically significant hemodynamic events. Most patients did not experience an event and those who did most frequently did so in the first couple of hours of therapy.

Midodrine as an Adjuvant to Intravenous Vasopressor Agents in Adults With Resolving Shock: Systematic Review and Meta-Analysis.

PURPOSE: To evaluate the effects of midodrine in addition to intravenous vasopressor therapy on outcomes in adults recovering from shock. MATERIALS AND METHODS: PubMed, Scopus, Clinicaltrials.gov, and published abstracts were searched from inception to November 2018 for studies comparing outcomes in shock after midodrine initiation versus no midodrine. RESULTS: Three studies with 2533 patients were included. Patients in whom midodrine was added to intravenous vasopressor therapy compared to intravenous vasopressor therapy alone experienced similar intensive care unit (ICU; mean difference [MD]: 1.38 days, 95% confidence interval [CI]: -3.48 to 6.23, I2 = 93%) and hospital lengths of stay (MD: 4.37 days, 95% CI: -3.45 to 12.19, I2 = 93%) and intravenous vasopressor duration after midodrine initiation (MD: 7.28 days, 95% CI: -0.86 to 15.41, I2 = 97%). Mortality was similar between groups (odds ratio: 0.74, 95% CI: 0.44-1.27, I2 = 65%). Qualitative assessment of reporting biases revealed minimal location bias, moderate selective outcome reporting bias, no selective analysis reporting bias, and no conflict of interest bias. CONCLUSIONS: Midodrine had no effect on ICU or hospital length of stay. These results were highly susceptible to the study heterogeneity and availability. Future investigation into standardized initiation of midodrine at an adequate dosage with an expedited titration strategy is needed in order to assess the utility of this strategy in shock management.

Evaluation of Medication Errors at the Transition of Care From an ICU to Non-ICU Location.

OBJECTIVES: To determine the point prevalence of medication errors at the time of transition of care from an ICU to non-ICU location and assess error types and risk factors for medication errors during transition of care. DESIGN: This was a multicenter, retrospective, 7-day point prevalence study. SETTING: Fifty-eight ICUs within 34 institutions in the United States and two in the Netherlands. PATIENTS: Nine-hundred eighty-five patients transferred from an ICU to non-ICU location. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 985 patients transferred, 450 (45.7%) had a medication error occur during transition of care. Among patients with a medication error, an average of 1.88 errors per patient (SD, 1.30; range, 1-9) occurred. The most common types of errors were continuation of medication with ICU-only indication (28.4%), untreated condition (19.4%), and pharmacotherapy without indication (11.9%). Seventy-five percent of errors reached the patient but did not cause harm. The occurrence of errors varied by type and size of institution and ICU. Renal replacement therapy during ICU stay and number of medications ordered following transfer were identified as factors associated with occurrence of error (odds ratio, 2.93; 95% CI, 1.42-6.05; odds ratio 1.08, 95% CI, 1.02-1.14, respectively). Orders for anti-infective (odds ratio, 1.66; 95% CI, 1.19-2.32), hematologic agents (1.75; 95% CI, 1.17-2.62), and IV fluids, electrolytes, or diuretics (odds ratio, 1.73; 95% CI, 1.21-2.48) at transition of care were associated with an increased odds of error. Factors associated with decreased odds of error included daily patient care rounds in the ICU (odds ratio, 0.15; 95% CI, 0.07-0.34) and orders discontinued and rewritten at the time of transfer from the ICU (odds ratio, 0.36; 95% CI, 0.17-0.73). CONCLUSIONS: Nearly half of patients experienced medication errors at the time of transition of care from an ICU to non-ICU location. Most errors reached the patient but did not cause harm. This study identified risk factors upon which risk mitigation strategies should be focused.

Norepinephrine and Vasopressin Compared With Norepinephrine and Epinephrine in Adults With Septic Shock.

Background: The optimal adjuvant vasopressor to norepinephrine in septic shock remains controversial. Objective: To compare durations of shock-free survival between adjuvant vasopressin and epinephrine. Methods: A retrospective, single-center, matched cohort study of adults with septic shock refractory to norepinephrine was conducted. Patients receiving norepinephrine not at target mean arterial pressure (MAP; 65 mm Hg) were initiated on vasopressin or epinephrine to raise MAP to target. Vasopressin-exposed patients were matched to epinephrine-exposed patients using propensity scores. Mortality outcomes were examined using multivariable Poisson regression with robust variance estimation. Results: Of 166 patients, 96 (entire cohort) were included in the propensity score-matched cohort. Shock-free survival durations in the first 7 days were similar between epinephrine- and vasopressin-exposed patients in the matched cohort (median = 13.2 hours, interquartile range [IQR] = 0-121.0, vs median = 41.3 hours, IQR = 0-125.9; P = 0.51). Seven- and 28-day mortality rates were similar in the matched cohort (7-day: 47.9% vs 39.6%, P = 0.35; 28-day: 56.3% vs 58.3%, P = 0.84). Mortality rates were similar between epinephrine- and vasopressin-exposed patients in propensity score-matched regression models with and without adjustments at 7 (relative risk [RR] = 1.28, 95% CI = 0.92-1.79; RR = 1.21, 95% CI = 0.81-1.81) and 28 days (RR = 1.04, 95% CI = 0.81-1.34; RR = 0.96, 95% CI = 0.69-1.34). Conclusion and Relevance: Shock-free survival durations were similar in matched epinephrine- and vasopressin-exposed groups. Adjuvant epinephrine or vasopressin alongside norepinephrine to raise MAP to target requires further investigation.

Systematic Review of the Clinical Utility of Methicillin-Resistant Staphylococcus aureus (MRSA) Nasal Screening for MRSA Pneumonia.

OBJECTIVE: To describe the diagnostic performance characteristics of methicillin-resistant Staphylococcus aureus (MRSA) nasal screening for patients with pneumonia. DATA SOURCES: PubMed and Scopus were searched from 1 January 1990 to 12 December 2018 using terms methicillin-resistant Staphylococcus aureus AND (screening OR active surveillance OR surveillance culture OR targeted surveillance OR chromogenic OR PCR OR polymerase chain reaction OR rapid test) AND (nares OR nasal) AND (pneumonia OR respiratory). STUDY SELECTION AND DATA EXTRACTION: Relevant studies in humans and English were considered. DATA SYNTHESIS: In all, 19 studies, including 21 790 patients, were included. Nasal screening for MRSA had a high negative predictive value (NPV; 76% to 99.4% for relevant studies) across all types of pneumonia. Time from nasal screening to culture varied across studies. Relevance to Patient Care and Clinical Practice: MRSA nasal screening has a high NPV for MRSA involvement in pneumonia. Utilizing this test for antimicrobial stewardship program (ASP) purposes can provide a valuable tool for reducing unwarranted anti-MRSA agents and may provide additional cost benefits. A cutoff of 7 days between nasal swab and culture or infection onset seems most appropriate for use of this test for anti-MRSA agent de-escalation for ASP purposes. CONCLUSIONS: Consideration for the inclusion of the utility of MRSA nasal screening in MRSA pneumonia should be made for future pneumonia and ASP guidelines. Additional studies are warranted to fully evaluate specific pneumonia classifications, culture types, culture timing, and clinical outcomes associated with the use of this test in patients with pneumonia.

Discontinuation of Vasopressin Before Norepinephrine in the Recovery Phase of Septic Shock.

BACKGROUND: Guidance for the discontinuation of vasopressors in the recovery phase of septic shock is limited. Norepinephrine is more easily titrated; however, septic shock is a vasopressin deficient state, which exogenous vasopressin endeavors to resolve. Discontinuation of vasopressin before norepinephrine may result in clinically significant hypotension. METHODS: This retrospective, cohort study compared discontinuation of norepinephrine and vasopressin in medically, critically ill patients in the recovery phase of septic shock from May 2014 to June 2016. Difference in clinically significant hypotension after norepinephrine or vasopressin discontinuation was evaluated with χ2 test. Linear regression was performed, examining the effect of agent discontinuation on clinically significant hypotension. Baseline variables were examined for a bivariate relationship with clinically significant hypotension; those with P < .2 were included in the model. RESULTS: Vasopressin was discontinued first or last in 62 and 92 patients, respectively. Sequential Organ Failure Assessment scores at 72 hours (7.9 vs 7.6, P = .679) were similar. In unadjusted analysis, when vasopressin was discontinued first, more clinically significant hypotension developed (10.9% vs 67.8%, P < .001). There was no difference in intensive care unit (174 vs 216 hours, P = .178) or hospital duration (470 vs 473 hours, P = .977). In adjusted analyses, discontinuing vasopressin first was associated with increased clinically significant hypotension (odds ratio [OR]: 13.837, 95% confidence interval [CI]: 3.403-56.250, P < .001) but not in-hospital (OR: 0.659, 95% CI: 0.204-2.137, P = .488) or 28-day mortality (OR: 0.215, 95% CI: 0.037-1.246, P = .086). CONCLUSION: Adult patients receiving norepinephrine and vasopressin in the resolving phase of septic shock may be less likely to develop clinically significant hypotension if vasopressin is the final vasopressor discontinued.

Effectiveness and Safety of Magnesium Replacement in Critically Ill Patients Admitted to the Medical Intensive Care Unit in an Academic Medical Center: A Retrospective, Cohort Study.

BACKGROUND: "Rules of thumb" for the replacement of electrolytes, including magnesium, in critical care settings are used, despite minimal empirical validation of their ability to achieve a target serum concentration. This study's purpose was to evaluate the effectiveness and safety surrounding magnesium replacement in medically, critically ill patients with mild-to-moderate hypomagnesemia. METHODS: This was a single-center, retrospective, observational evaluation of episodes of intravenous magnesium replacement ordered for patients with mild-to-moderate hypomagnesemia (1.0-1.9 mEq/L) admitted to a medical intensive care unit from May 2014 to April 2016. The primary effectiveness outcome, achievement of target serum magnesium concentration (≥2 mEq/L) compared to expected achievement using a "rule of thumb" estimation that 1 g intravenous magnesium sulfate raises the magnesium concentration 0.15 mEq/L, was tested using 1-sample z test. Logistic regression analysis was conducted to assess the effect of infusion rate on target achievement. RESULTS: Of 152 days on which magnesium replacements were provided for 72 patients, a follow-up serum magnesium concentration was checked within 24 hours in 89 (58.6%) episodes. Of these 89 episodes, serum magnesium concentration reached target in only 49 (59.8%) episodes compared to an expected 89 (100%; P < .0001). There was no significant association between infusion rate and achievement of the target serum magnesium concentration (odds ratio: 0.962, 95% confidence interval: 0.411-2.256). CONCLUSIONS: Medically, critically ill patients who received nonprotocolized magnesium replacement achieved the target serum magnesium concentration less frequently than the "rule of thumb" estimation predicted.