Evaluating Vasopressor Discontinuation Strategies in Patients With Septic Shock on Concomitant Norepinephrine and Vasopressin Infusions

Musallam, Nadine; Altshuler, Diana; Merchan, Cristian; Zakhary, Bishoy; Aberle, Caitlin; Papadopoulos, John

doi:10.1177/1060028018765187

Cited by 28 publications

(54 citation statements)

References 21 publications

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“…These findings were reproduced by Musallam et al, in which they noted a 7-fold increased risk in hypotension when vasopressin was discontinued first [7]. While the findings of our review did not substantiate these claims, we discovered a longer duration of vasopressor therapy in the cohort of patients in which vasopressin was discontinued first, which may correlate with relative vasopressin deficiency in these patients leading to prolonged hypotension.…”

Section: Discussionsupporting

confidence: 68%

“…Patients can continue to experience clinically significant hypotension after vasopressor discontinuation which has been associated with poor outcomes [5][6]. Thus, the optimal approach to discontinuing vasopressors, especially for those patients that required multiple agents has been of question, with several hypotheses that continuing vasopressin therapy and discontinuing norepinephrine first may be beneficial in the likely setting of vasopressin deficiency that can persist for 36 to 96 hours [5,7].…”

Section: Introductionmentioning

confidence: 99%

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Impact of Vasopressor Initiation and Discontinuation Sequence on Mortality in Septic Shock: A Retrospective Review

Moyer¹,

McDaniel²,

Brown³

et al. 2020

SCR

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Background: Little data exists guiding clinicians on how or when to initiate and discontinue the second vasoactive agent in the setting of septic shock refractory to norepinephrine monotherapy. Methods: This retrospective cohort study evaluated patients with a primary diagnosis of septic shock admitted to the intensive care unit receiving norepinephrine in addition to concomitant vasopressors. The primary endpoint was the incidence of all-cause in-hospital mortality when adding adjunctive vasopressors to norepinephrine either before the dose reached 2 mcg/kg/min (early adjunctive vasopressor) or after (late adjunctive vasopressor). Secondary endpoints included the incidence of clinically significant hypotension when discontinuing norepinephrine before or after vasopressin in the same population. Results: Forty-six patients were included (early adjunctive vasopressor [n=36]; late adjunctive vasopressor [n=10]), with a median age of 69 years and APACHE II score of 27. Fewer patients in the early adjunctive vasopressor cohort had malignancy prior to admission (16.7% vs. 60%, p=0.0117), however, more patients were managed in the surgical ICU (44.4% vs. 0%, p=0.0202) with intra-abdominal infection (33.3% vs. 0%, p=0.0439). The primary endpoint of all-cause in-hospital mortality was not statistically different between the early and late adjunctive vasopressor groups (75% vs. 90%, respectively, p=0.4203). Longer ICU and hospital length of stay in the early adjunctive vasopressor cohort was observed (9 days vs 3 days, p=0.0061; 11 days vs 3 days, p=0.0026, respectively). Twenty-two patients were included in analysis of vasopressor discontinuation sequence with no significant differences in mortality, incidence of hypotension, or ICU/hospital length of stay. Conclusion: Among patients with septic shock on multiple vasopressors, addition of adjunctive vasopressor before reaching a norepinephrine dose of 2 mcg/kg/min was associated with longer in-hospital and ICU survival but exhibited no difference in overall mortality. Discontinuation of vasopressin before norepinephrine led to longer total vasopressor duration without a difference in rates of hypotension. Future prospective studies are warranted.

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Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Impact of Vasopressor Initiation and Discontinuation Sequence on Mortality in Septic Shock: A Retrospective Review

Moyer¹,

McDaniel²,

Brown³

et al. 2020

SCR

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“…9-11,21,24,28,30 Additional areas with unclear clinical data where cost savings could be realized include initiating vasopressin at a dosage of 0.03 units/min (as opposed to 0.04 units/min) and discontinuing vasopressin prior to norepinephrine. [12][13][14][15][16]31 Although vasopressin up to 0.06 units/min has been used with minimal safety concerns, 24 the seminal trial used 0.03 units/min, 26 which is the guideline-recommended dosage. 1 Evaluations of adjuvant vasopressor strategies for patients in whom norepinephrine monotherapy is inadequate, the discontinuation order of vasoactive medications, and the Those surveyed were asked to indicate their agreement or disagreement with the use of vasopressin for the listed indications for patients with septic shock while considering both available evidence for treatment and cost and while just considering the available evidence.…”

Section: Discussionmentioning

confidence: 99%

“…8 Other initiatives to identify optimal strategies for vasopressin use in septic shock that were evaluated for effects on clinical outcomes have included restriction of vasopressin use in septic shock until the norepinephrine infusion rate is above 50 mcg/min; 9 early, concomitant initiation of norepinephrine and vasopressin; 10,11 and the order of vasopressin discontinuation in resolving septic shock. [12][13][14][15][16] Many of these studies evaluated a small number of clinicians/institutions and failed to evaluate some of the clinical scenarios where vasopressin is often used (eg, severe acidemia, elevated lactate).…”

Section: Introductionmentioning

confidence: 99%

Perceptions regarding vasopressin use and practices in septic shock, and cost containment strategies

Hammond

Rech

Daley

et al. 2019

J Am Coll Clin Pharm

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Background Clinician preferences and practices regarding appropriate vasopressin use in light of its increased acquisition cost secondary to rebranding has not been evaluated or described since the most recent iteration of the Surviving Sepsis Campaign Guideline was published. Objective To assess vasopressin cost containment initiatives and pharmacists' opinions regarding appropriate vasopressin use. Methods A scenario‐based survey was distributed to critical care and emergency medicine pharmacists. Responses were characterized using frequency and descriptive statistics. Categorical variables between those who implemented changes (Vasopressin Cost Consideration) and those who did not (Usual Care) were compared using chi‐square or Fisher's exact tests. McNemar's test was used to compare responses in clinical scenarios between Vasopressin Cost Consideration and Usual Care groups. Results Among 1757 pharmacists surveyed, 200 (11.3%) responded. When respondents considered vasopressin cost and evidence (vs evidence alone), fewer respondents would use vasopressin adjunctively with norepinephrine (21% vs 26.6%, P = 0.031), to raise mean arterial pressure compared with epinephrine (65.2% vs 72.3%, P = 0.012), or to reduce norepinephrine infusion rates (71.4% vs 81.4%, P < 0.001), but would use with steroids (62.4% vs 28.3%, P < 0.001). Most (72%) respondents had implemented vasopressin cost containment and/or education initiatives. The Vasopressin Cost Consideration group respondents were more likely to initiate vasopressin at 0.03 units/minute without titrating (47.9% vs 33.9%, P = 0.045). Conclusion Since vasopressin was generically rebranded, most institutions have implemented at least one initiative to reduce vasopressin use and/or educate clinicians about its appropriate use. When vasopressin acquisition costs were considered, pharmacists recommended its use less frequently, particularly in clinical scenarios where its use is controversial.

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“…Several studies have demonstrated a higher incidence of hypotension after vasopressin discontinuation compared with NE discontinuation. [29][30][31][32][33] Patient demographics, vasopressor utilization, and clinical outcomes were similar to the overall cohort (Tables S1 and S2, Supporting Information).…”

Section: Discussionmentioning

confidence: 71%

Utilization of vasopressin before and after protocol implementation in a surgical intensive care unit

Smith

Rumbaugh

2019

J Am Coll Clin Pharm

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Introduction Vasopressin is recommended for management of septic shock refractory to fluid challenge and norepinephrine. Controversy exists over when to add vasopressin to norepinephrine treatment. Due to the rising cost of vasopressin and the lack of mortality benefit, the surgical intensive care unit (SICU) at Vanderbilt University Medical Center implemented a protocol for vasopressin use with the purpose of decreasing utilization and cost. Objective The purpose of this study was to characterize vasopressin utilization and evaluate adherence to this protocol. Methods Through a retrospective, observational analysis, adult patients admitted to the SICU who received vasopressin during the 11 months before and after protocol implementation in August 2015 were identified. The primary outcome was vasopressin usage per patient. Secondary outcomes included norepinephrine use, vasopressin cost, and protocol adherence. Results During the pre‐ and post‐protocol periods, 144 of 1788 admitted patients (8%) and 119 of 1845 admitted patients (6%) received vasopressin, respectively. The total duration of vasopressin infusion during hospitalization was similar before and after protocol implementation (20 vs 18 hours, P = 0.526), but vasopressin was both added and discontinued when norepinephrine was infusing at a higher rate (added at 12 vs 18 mcg/min, P < 0.001; discontinued at 0.5 vs 6.0 mcg/min, P < 0.001). Norepinephrine was infused for a longer duration post protocol implementation (31 vs 57 hours, P < 0.001). After implementation, a protocol violation occurred in 59 patients (50%); however, 59% of these were related to vasopressin initiation in the operating room. Thirty‐two patients (27%) experienced a SICU‐related violation, with the most common type being discontinuation of norepinephrine prior to vasopressin. Conclusion Implementation of a vasopressin utilization protocol in a SICU resulted in more selective usage of vasopressin and a similar duration of infusion when it was utilized. Protocol adherence was nearly 75%, exposing some opportunities for continued education and improvement.

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Evaluating Vasopressor Discontinuation Strategies in Patients With Septic Shock on Concomitant Norepinephrine and Vasopressin Infusions

Abstract: Among septic shock patients on concomitant NE and VP, discontinuation of VP first was associated with an increased incidence of hypotension; future prospective control trials are warranted.

Cited by 28 publications

References 21 publications

Impact of Vasopressor Initiation and Discontinuation Sequence on Mortality in Septic Shock: A Retrospective Review

Impact of Vasopressor Initiation and Discontinuation Sequence on Mortality in Septic Shock: A Retrospective Review

Perceptions regarding vasopressin use and practices in septic shock, and cost containment strategies

Utilization of vasopressin before and after protocol implementation in a surgical intensive care unit

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