Prospective randomized double-blind study to evaluate the superiority of Vasopressin versus Norepinephrine in the management of the patient at renal risk undergoing cardiac surgery with cardiopulmonary bypass (NOVACC trial).

BACKGROUND: Cardiac surgery-associated acute kidney injury (CS-AKI) affects up to 30% of patients, increasing morbidity and healthcare costs. This condition results from complex factors like ischemia-reperfusion injury and renal hemodynamic changes, often exacerbated by surgical procedures. Norepinephrine, commonly used in cardiac surgeries, may heighten the risk of CS-AKI. In contrast, vasopressin, a noncatecholaminergic agent, shows potential in preserving renal function by favorably affecting renal hemodynamic. Preliminary findings, suggest vasopressin could reduce the incidence of CS-AKI compared to norepinephrine. Additionally, vasopressin is linked to a lower incidence of postoperative atrial fibrillation, another factor contributing to longer hospital stays and higher costs. This study hypothesizes that vasopressin could effectively reduce CS-AKI occurrence and severity by optimizing renal perfusion during cardiac surgeries. STUDY DESIGN: The NOVACC trial (NCT05568160) is a multicenter, randomized, double blinded superiority-controlled trial testing the superiority of vasopressin over norepinephrine in patients scheduled for cardiac surgery with cardiopulmonary bypass (CPB). The primary composite end point is the occurrence of acute kidney injury and death. The secondary end points are neurological, cardiologic, digestive, and vasopressor related complications at day 7, day 30, day 90, hospital and intensive care unit lengths of stay, medico-economic costs at day 90. CONCLUSION: The NOVACC trial will assess the effectiveness of vasopressin in cardiac surgery with CPB in reducing acute kidney injury, mortality, and medical costs. CLINICAL TRIAL REGISTRATION: NCT05568160.

Vasopressin in newborns with refractory acute pulmonary hypertension.

BACKGROUND: Acute pulmonary hypertension (aPH) in newborns can be life threatening and challenging to manage. In newborns with refractory aPH, there is currently limited therapeutic agents. METHODS: Retrospective single-center cohort study in newborns less than one month old who were treated with vasopressin for a minimum of one hour in the context of refractory aPH in the neonatal and pediatric intensive care units of a tertiary university center between 2016 and 2022. The objective was to evaluate the efficacy and safety of vasopressin in newborns as an adjuvant treatment for refractory aPH. RESULTS: Twenty-five patients met inclusion criteria. In patients who received vasopressin, oxygenation index improved from 28.4 to 14.4 (p = 0.004) after twelve hours of continuous infusion. Oxygen requirements (FiO2) decreased from 0.91 to 0.50 (p = 0.004) and mean arterial pressure increased from 41 to 51 mmHg (p = 0.001). In our cohort, 68% of patients presented an episode of hyponatremia (serum sodium <130 mmol/L). CONCLUSIONS: The use of vasopressin may be associated with improvement in oxygenation and hemodynamic status of neonatal patients with aPH refractory to initial therapy. Further prospective studies are needed to establish the safety profile of vasopressin in newborns, particularly in preterm infants. IMPACT: Vasopressin may be an effective cardiotropic agent to improve oxygenation and hemodynamic status in newborns with acute pulmonary hypertension. Careful monitoring of serum sodium levels are warranted in newborns who are receiving vasopressin infusion. This provides additional evidence for the consideration of vasopressin in newborns with acute pulmonary hypertension refractory to inhaled nitric oxide.

Comparison of Early Versus Late Adjunctive Vasopressin and Corticosteroids in Patients With Septic Shock.

BACKGROUND: Vasopressin (VP) and hydrocortisone (HC) have been shown to improve outcomes in patients with septic shock. However, there is very little literature addressing the impact of the timing of the combination. OBJECTIVE: This study was conducted to evaluate the impact of early versus late initiation of both VP and HC on time to shock reversal in septic shock patients. METHODS: This was a retrospective study conducted at a tertiary academic medical center. Data were collected from system-generated reports, which were used to identify patients with septic shock who were admitted to an intensive care unit (ICU) and received both VP and HC. The primary endpoint was time to shock reversal. Patients were divided into the "early" group if both VP and HC were initiated within 12 hours of vasopressor initiation or into the "late" group if either VP or HC (or both agents) were initiated after 12 hours of vasopressor initiation. RESULTS: A total of 122 patients were included in the analysis. Early initiation was associated with a shorter time to shock reversal (34 hours vs 65 hours; P = 0.012) compared to late initiation. There were no differences in ICU length of stay, mortality, the number patients requiring renal replacement therapy, or the duration of mechanical ventilation in either group. CONCLUSION AND RELEVANCE: Our study addressed a major gap in the literature and suggests that adding the combination of VP and HC within 12 hours of septic shock may be associated with improved patient outcomes.

Effect of Early Administration of Vasopressin on New-Onset Arrhythmia Development in Patients With Septic Shock: A Retrospective, Observational Cohort Study.

Background: Adjunctive vasopressin use in septic shock reduces catecholamine requirements and is associated with a lower incidence of new-onset arrhythmias (NOAs). The association of vasopressin timing on NOA development is ill-described. Objective: To determine whether early administration of vasopressin was associated with a lower incidence of NOA in septic shock patients. Methods: A retrospective analysis of intensive care unit (ICU) patients at a large, academic medical center. Septic shock patients who required vasopressin and norepinephrine were eligible for inclusion. Patients were excluded for receipt of other vasoactive agents, history of cardiac arrhythmias, or outside hospital admission. Early vasopressin was defined as receipt within 6 hours of septic shock onset. The primary outcome was incidence of NOA. Results: In total, 436 patients, 220 (50.4%) in the early and 216 (49.6%) in the late vasopressin group, were included. Early vasopressin was not associated with a lower incidence of NOA compared with late vasopressin (9% vs 7%, median absolute difference [95% confidence interval, CI]: -2.1 [-7.2, 3.0], P = 0.41). Early vasopressin patients were observed to have shorter shock duration (2 vs 4 days, median absolute difference [95% CI]: 2 [1, 2], P < 0.001), and ICU length of stay (6 vs 7 days, median absolute difference [95% CI]: 1 [0, 2], P = 0.02). Conclusions and Relevance: Early vasopressin use was not associated with a lower incidence of NOA. Additional studies are needed to elucidate the effect of vasopressin timing on NOA and other clinical outcomes.

Does Early Vasopressin in Septic Shock Improve Outcomes? An Important Piece to This Emerging Puzzle Has Arrived.

In this month's Annals of Pharmacotherapy, the largest observational study assessing the early versus later use of vasopressin has been published. When this new study is combined with the other available observational studies, there are 2 important outcomes to focus on. When all the observational studies are pooled together, no reduction in new onset arrhythmias is seen (odds ratio [OR] = 0.91, 95% confidence interval [CI] = 0.41-1.95) with early versus late vasopressin use while the reduction in renal replacement therapy just missed statistical significance (OR = 0.56, 95% CI = 0.32-1.00). Early vasopressin likely does not reduce new onset arrhythmias versus later use but might reduce the need for renal replacement therapy.

Mortality, morbidity & clinical outcome with different types of vasopressors in out of hospital cardiac arrest patients- a systematic review and meta-analysis.

BACKGROUND & OBJECTIVE: Despite their continued use, the effectiveness and safety of vasopressors in post-cardiac arrest patients remain controversial. This study examined the efficacy of various vasopressors in cardiac arrest patients in terms of clinical, morbidity, and mortality outcomes. METHODS: A comprehensive literature search was performed using online databases (MeSH terms: MEDLINE (Ovid), CENTRAL (Cochrane Library), Embase (Ovid), CINAHL, Scopus, and Google Scholar) from 1997 to 2023 for relevant English language studies. The primary outcomes of interest for this study included short-term survival leading to death, return of spontaneous circulation (ROSC), survival to hospital discharge, neurological outcomes, survival to hospital admission, myocardial infarction, and incidence of arrhythmias. RESULTS: In this meta-analysis, 26 studies, including 16 RCTs and ten non-RCTs, were evaluated. The focus was on the efficacy of epinephrine, vasopressin, methylprednisolone, dopamine, and their combinations in medical emergencies. Epinephrine treatment was associated with better odds of survival to hospital discharge (OR = 1.52, 95%CI [1.20, 1.94]; p < 0.001) and achieving ROSC (OR = 3.60, 95% CI [3.45, 3.76], P < 0.00001)) over placebo but not in other outcomes of interest such as short-term survival/ death at 28-30 days, survival to hospital admission, or neurological function. In addition, our analysis indicates non-superiority of vasopressin or epinephrine vasopressin-plus-epinephrine therapy over epinephrine monotherapy except for survival to hospital admission where the combinatorial therapy was associated with better outcome (0.76, 95%CI [0.64, 0.92]; p = 0.004). Similarly, we noted the non-superiority of vasopressin-plus-methylprednisolone versus placebo. Finally, while higher odds of survival to hospital discharge (OR = 3.35, 95%CI [1.81, 6.2]; p < 0.001) and ROSC (OR = 2.87, 95%CI [1.97, 4.19]; p < 0.001) favoring placebo over VSE therapy were observed, the risk of lethal arrhythmia was not statistically significant. There was insufficient literature to assess the effects of dopamine versus other treatment modalities meta-analytically. CONCLUSION: This meta-analysis indicated that only epinephrine yielded superior outcomes among vasopressors than placebo, albeit limited to survival to hospital discharge and ROSC. Additionally, we demonstrate the non-superiority of vasopressin over epinephrine, although vasopressin could not be compared to placebo due to the paucity of data. The addition of vasopressin to epinephrine treatment only improved survival to hospital admission.

Outcomes of Vasopressin-Receptor Agonists Versus Norepinephrine in Adults With Perioperative Hypotension: A Systematic Review.

Consensus statements recommend the use of norepinephrine and/or vasopressin for hypotension in cardiac surgery. However, there is a paucity of data among other surgical subgroups and vasopressin analogs. Therefore, the authors conducted a systematic review of randomized controlled trials (RCTs) to compare vasopressin-receptor agonists with norepinephrine for hypotension among those undergoing surgery with general anesthesia. This review was registered prospectively (CRD42022316328). Literature searches were conducted by a medical librarian to November 28, 2023, across MEDLINE, EMBASE, CENTRAL, and Web of Science. The authors included RCTs enrolling adults (≥18 years of age) undergoing any surgery under general anesthesia who developed perioperative hypotension and comparing vasopressin receptor agonists with norepinephrine. The risk of bias was assessed by the Cochrane risk of bias tool for randomized trials (RoB-2). Thirteen (N = 719) RCTs were included, of which 8 (n = 585) enrolled patients undergoing cardiac surgery. Five trials compared norepinephrine with vasopressin, 4 trials with terlipressin, 1 trial with ornipressin, and the other 3 trials used vasopressin as adjuvant therapy. There was no significant difference in all-cause mortality. Among patients with vasoplegic shock after cardiac surgery, vasopressin was associated with significantly lower intensive care unit (N = 385; 2 trials; mean 100.8 v 175.2 hours, p < 0.005; median 120 [IQR 96-168] v 144 [96-216] hours, p = 0.007) and hospital lengths of stay, as well as fewer cases of acute kidney injury and atrial fibrillation compared with norepinephrine. One trial also found that terlipressin was associated with a significantly lower incidence of acute kidney injury versus norepinephrine overall. Vasopressin and norepinephrine restored mean arterial blood pressure with no significant differences; however, the use of vasopressin with norepinephrine was associated with significantly higher mean arterial blood pressure versus norepinephrine alone. Further high-quality trials are needed to determine pooled treatment effects, especially among noncardiac surgical patients and those treated with vasopressin analogs.

Vasopressin Injection Purse-String Ectopic Resection technique for laparoscopic management of cornual ectopic pregnancy.

Although cornual pregnancy is a rare form of ectopic pregnancy, the associated mortality rate is considerably higher than that of ectopic pregnancy overall. Historically, cornual ectopic pregnancy has been treated via laparotomy. With advancements in technology, equipment, and technique, laparoscopy offers a safer approach for the management of cornual pregnancy. However, laparoscopy of this nature requires excellent technique. The Vasopressin Injection Purse-String Ectopic Resection technique serves as an effective strategy for the laparoscopic management of cornual ectopic pregnancy. First, dilute vasopressin is administered into the myometrium surrounding the pregnancy. Next, a purse-string stitch is placed in the myometrium circumferential to the pregnancy. Finally, the pregnancy is excised by cornual wedge resection, and the defect is repaired using the attached remaining suture from the purse-string stitch. The Figure shows the graphical depiction of the Vasopressin Injection Purse-String Ectopic Resection technique, and the Video shows a laparoscopic recording of the Vasopressin Injection Purse-String Ectopic Resection technique. Between 2012 and 2022, 17 patients underwent a laparoscopic cornual ectopic pregnancy resection at a high-volume academic hospital and its affiliated community hospital. This case series revealed a mean operative time of 107 minutes, with a mean estimated blood loss of 41 mL for nonruptured ectopic pregnancies and 412 mL for ruptured ectopic pregnancies. No case was converted to laparotomy. Our findings suggest that the integration of the vasopressin administration and the pursue-string stitch placement minimizes blood loss and mitigates the risk of conversion to laparotomy for both nonruptured and ruptured cornual ectopic pregnancies.

Timing of vasopressin initiation and mortality in patients with septic shock: analysis of the MIMIC-III and MIMIC-IV databases.

BACKGROUND: vasopressin is commonly used as a second-line vasopressor for patients with septic shock, but the optimal timing of initiation is uncertain. This study was designed to investigate when vasopressin initiation may be beneficial for 28-day mortality in septic shock patients. METHODS: This was a retrospective observational cohort study from the MIMIC-III v1.4 and MIMIC-IV v2.0 databases. All adults diagnosed with septic shock according to Sepsis-3 criteria were included. Patients were stratified into two groups based on norepinephrine (NE) dose at the time of vasopressin initiation, defined as the low doses of NE group (NE<0.25 µg/kg/min) and the high doses of NE group (NE ≥ 0.25 µg/kg/min). The primary end-point was 28-day mortality after diagnosis of septic shock. The analysis involved propensity score matching (PSM), multivariable logistic regression, doubly robust estimation, the gradient boosted model, and an inverse probability-weighting model. RESULTS: A total of 1817 eligible patients were included in our original cohort (613 in the low doses of NE group and 1204 in the high doses of NE group). After 1:1 PSM, 535 patients from each group with no difference in disease severity were included in the analysis. The results showed that vasopressin initiation at low doses of NE was associated with reduced 28-day mortality (odds ratio [OR] 0.660, 95% confidence interval [CI] 0.518-0.840, p < 0.001). Compared with patients in the high doses of NE group, patients in the low doses of NE group received significantly shorter duration of NE, with less intravenous fluid volume on the first day after initiation of vasopressin, more urine on the second day, and longer mechanical ventilation-free days and CRRT-free days. Nevertheless, there were no significant differences in hemodynamic response to vasopressin, duration of vasopressin, and ICU or hospital length of stay. CONCLUSIONS: Among adults with septic shock, vasopressin initiation when low-dose NE was used was associated with an improvement in 28-day mortality.

Timing of Vasopressin Addition to Norepinephrine and Efficacy Outcomes in Patients With Septic Shock.

BACKGROUND: Current guidelines recommend norepinephrine as the first-line vasopressor in septic shock followed by addition of vasopressin to achieve a goal mean arterial pressure. Limited evidence exists evaluating how the timing of vasopressin addition affects clinical outcomes in septic shock. OBJECTIVE: The objective of this study was to determine whether the timing of the addition of vasopressin to norepinephrine affects shock resolution. METHODS: This was a multi-site, single system, retrospective cohort, institutional review board (IRB)-approved study examining adult patients with septic shock who received norepinephrine and vasopressin. Patients were divided and statistically analyzed in two subgroups: early vasopressin addition (<3 hours) and late vasopressin addition (≥3 hours). The primary outcome was time to shock resolution, defined as vasopressor free for at least 24 hours. Secondary outcomes included norepinephrine dose at 3 hours after initiation of vasopressin, in-hospital mortality, and intensive care unit length of stay. RESULTS: A total of 243 patients were included in this study. A statistically significant decrease in time to shock resolution was observed in the early vasopressin addition group compared to the late vasopressin addition group (37.6 hours vs 60.7 hours; adjusted hazard ratio [HR]: 2.07 [1.48-2.89; P = <0.001]). The early addition of vasopressin did not affect norepinephrine dose or in-hospital mortality but did lead to a decreased intensive care unit (ICU) length of stay (4.3 days vs 5.3 days, P = 0.02). CONCLUSION AND RELEVANCE: Addition of vasopressin to norepinephrine within 3 hours was associated with a faster time to shock resolution. These findings suggest a potential for improved clinical outcomes with earlier vasopressin addition.

The Vasopressin Loading for Refractory septic shock (VALOR) study: a prospective observational study.

BACKGROUND: Vasopressin is a second-line vasoactive agent for refractory septic shock. Vasopressin loading is not generally performed because of the lack of evidence for its effects and safety. However, based on our previous findings, we hypothesized it can predict the responsibility to vasopressin infusion with safety, and prospectively examined it in the present study. METHODS: Vasopressin loading was performed via the intravenous administration of a bolus of 1 U, followed by its continuous infusion at 1U/h in patients with septic shock treated with ≥ 0.2 µg/kg/min noradrenaline. An arterial pressure wave analysis was conducted, and endocrinological tests were performed immediately prior to vasopressin loading. We classified patients into responders/non-responders based on mean arterial pressure (MAP) changes after vasopressin loading. Based on our previous findings, the lower tertile of MAP changes was selected as the cut-off. The change in the catecholamine index (CAI) after 6 h was assigned as the primary outcome. Digital ischemia, mesenteric ischemia, and myocardial ischemia during the admission period were prospectively and systematically recorded as adverse events. RESULTS: Ninety-two patients were registered during the study period and examined. Sixty-two patients with a MAP change > 22 mmHg were assigned as responders and the others as non-responders. Blood adrenocorticotropic hormone levels were significantly higher in non-responders. Stroke volume variations were higher in responders before loading, while stroke volume and dP/dtmax were higher in responders after loading. Median CAI changes were - 10 in responders and 0 in non-responders, which was significantly lower in the former (p < 0.0001). AUROC of MAP change with vasopressin loading to predict CAI change < 0 after continuous infusion was 0.843 with sensitivity of 0.92 and specificity of 0.77. Ischemia events were observed in 5 cases (5.4%). CONCLUSIONS: Vasopressin loading may be safely introduced for septic shock. Vasopressin loading may be used to predict responses to its continuous infusion and select appropriate strategies to increase blood pressure.

An updated "norepinephrine equivalent" score in intensive care as a marker of shock severity.

Vasopressors and fluids are the cornerstones for the treatment of shock. The current international guidelines on shock recommend norepinephrine as the first-line vasopressor and vasopressin as the second-line vasopressor. In clinical practice, due to drug availability, local practice variations, special settings, and ongoing research, several alternative vasoconstrictors and adjuncts are used in the absence of precise equivalent doses. Norepinephrine equivalence (NEE) is frequently used in clinical trials to overcome this heterogeneity and describe vasopressor support in a standardized manner. NEE quantifies the total amount of vasopressors, considering the potency of each such agent, which typically includes catecholamines, derivatives, and vasopressin. Intensive care studies use NEE as an eligibility criterion and also an outcome measure. On the other hand, NEE has several pitfalls which clinicians should know, important the lack of conversion of novel vasopressors such as angiotensin II and also adjuncts such as methylene blue, including a lack of high-quality data to support the equation and validate its predictive performance in all types of critical care practice. This review describes the history of NEE and suggests an updated formula incorporating novel vasopressors and adjuncts.

Vasopressin Response and Clinical Trajectory in Septic Shock Patients.

BACKGROUND: In septic shock, vasopressors aim to improve tissue perfusion and prevent persistent organ dysfunction, a characteristic of chronic critical illness (CCI). Adjunctive vasopressin is often used to decrease catecholamine dosage, but the association of vasopressin response with subsequent patient outcomes is unclear. We hypothesized vasopressin response is associated with favorable clinical trajectory. METHODS: We included patients with septic shock receiving vasopressin as a catecholamine adjunct in this retrospective cohort study. We defined vasopressin response as a lowering of the catecholamine dose required to maintain mean arterial pressure ≥65 mm Hg, 6 h after vasopressin initiation. Clinical trajectories were adjudicated as early death (ED; death before day 14), CCI (ICU stay ≥14 days with persistent organ dysfunction), or rapid recovery (RR; not meeting ED or CCI criteria). Trajectories were placed on an ordinal scale with ED the worst outcome, CCI next, and RR the best outcome. The association of vasopressin response with clinical trajectory was assessed with multivariable ordinal logistic regression. RESULTS: In total 938 patients were included; 426 (45.4%) were vasopressin responders. The most frequent trajectory was ED (49.8%), 29.7% developed CCI, and 20.5% had rapid recovery. In survivors to ICU day 14 (those without ED), 59.2% had CCI and 40.8% experienced RR. Compared with vasopressin non-responders, vasopressin responders less frequently experienced ED (42.5% vs. 55.9%) and more frequently experienced RR (24.6% vs. 17.0%; P < 0.01). After controlling for confounders, vasopressin response was independently associated with higher odds of developing a better clinical trajectory (OR 1.63; 95% CI 1.26-2.10). Medical patients most frequently developed ED and survivors more commonly developed CCI than RR; surgical patients developed the three trajectories with similar frequency (P < 0.01). CONCLUSIONS: Vasopressin responsive status was associated with improved clinical trajectory in septic shock patients. Early vasopressin response is a potential novel prognostic marker for short-term clinical trajectory.

Effect of early vasopressin combined with norepinephrine on short-term mortality in septic shock: A retrospective study based on the MIMIC-IV database.

BACKGROUND: Septic shock is a leading cause of death in intensive care units (ICUs), with short-term mortality rates of 35-40%. Vasopressin (AVP) is a second-line vasoactive agent for septic shock, and recent studies suggest that early AVP use can be beneficial. However, differences between early initiation of AVP combined with norepinephrine (NE) and nonearly AVP with NE are unclear. A retrospective cohort research was designed to explore the effects of early AVP initiation versus nonearly AVP initiation. METHODS: This retrospective single-center cohort study included adult patients with septic shock from the MIMIC (Medical Information Mart for Intensive Care)-IV database. According to whether AVP was used early in the ICU (intensive care unit), patients were assigned to the early- (within 6 h of septic shock onset) and non-early-AVP (at least 6 h after septic shock onset) groups. The primary outcome was 28-day mortality. The secondary outcomes were ICU and hospital mortality, the numbers of vasopressor-free and ventilation-free days at 28 days, ICU length of stay (LOS), hospital LOS, sequential organ failure assessment (SOFA) score on days 2 and 3, and renal replacement therapy (RRT) use on days 2 and 3. Univariate and multivariate cox proportional-hazards regression, propensity-score matching were used to analyze the differences between the groups. RESULTS: The study included 531 patients with septic shock: 331 (62.5%) in the early-AVP group and 200 (37.5%) in the non-early-AVP group. For 1:1 matching, 158 patients in the early-AVP group were matched with the same number of patients with nonearly AVP. Regarding the primary outcome, there was no significant difference between the early- and non-early-AVP groups in 28-day mortality (hazard ratio [HR] = 0.91, 95% confidence interval [CI] = 0.68-1.24). For the secondary outcomes, there were no differences between the early- and non-early-AVP groups in ICU mortality (HR = 0.95, 95% CI = 0.67-1.35), hospital mortality (HR = 0.95, 95% CI = 0.69-1.31), the numbers of vasopressor-free and ventilation-free days at 28 days, ICU LOS, hospital LOS, SOFA score on days 2 and 3, and RRT use on days 2 and 3. CONCLUSIONS: There was no difference in short-term mortality between early AVP combined with NE and nonearly AVP with NE in septic shock.

Association Between Vasopressin Rebranding and Utilization in Patients With Septic Shock.

OBJECTIVES: Vasopressin is suggested as an adjunct to norepinephrine in patients with septic shock. However, after vasopressin was rebranded in November 2014, its cost exponentially increased. Utilization patterns of vasopressin after its rebranding are unclear. The objective of this study was to determine if there is an association between the rebranding of vasopressin in November 2014 and its utilization in vasopressor-dependent patients with severe sepsis or septic shock. DESIGN: Retrospective, multicenter, database study between January 2010 and March 2017. SETTING: Premier Healthcare Database hospitals. PATIENTS: Adult patients admitted to an ICU with severe sepsis or septic shock, who received at least one vasoactive agent for two or more calendar days were included. INTERVENTIONS: The proportion of patients who received vasopressin and vasopressin cost was assessed before and after rebranding, and evaluated with segmented regression. MEASUREMENTS AND MAIN RESULTS: Among 294,733 patients (mean age, 66 ± 15 yr), 27.8% received vasopressin, and ICU mortality was 26.5%. The proportion of patients receiving vasopressin was higher after rebranding (31.2% postrebranding vs 25.8% prerebranding). Before vasopressin rebranding, the quarterly proportion of patients who received vasopressin had an increasing slope (prerebranding slope 0.41% [95% CI, 0.35-0.46%]), with no difference in slope detected after vasopressin rebranding (postrebranding slope, 0.47% [95% CI, 0.29-0.64%]). After vasopressin rebranding, mean vasopressin cost per patient was higher ($527 ± 1,130 vs $77 ± 160), and the quarterly slope of vasopressin cost was higher (change in slope $77.18 [95% CI, $75.73-78.61]). Total vasopressin billed cost postrebranding continually increased by ~$294,276 per quarter from less than $500,000 in Q4 2014 to over $3,000,000 in Q1 2017. CONCLUSIONS: After vasopressin rebranding, utilization continued to increase quarterly despite a significant increase in vasopressin cost. Vasopressin appeared to have price inelastic demand in septic shock.

Association of Catecholamine Dose, Lactate, and Shock Duration at Vasopressin Initiation With Mortality in Patients With Septic Shock.

OBJECTIVES: To determine the association of catecholamine dose, lactate concentration, and timing from shock onset at vasopressin initiation with in-hospital mortality. DESIGN: Retrospective, observational study using segmented and multivariable logistic regression to evaluate the associations of catecholamine dose, lactate concentration, and timing from shock onset at vasopressin initiation with in-hospital mortality. SETTING: Multiple hospitals within the Cleveland Clinic Health System. PATIENTS: Adult patients who met criteria for septic shock based on the U.S. Centers for Disease Control and Prevention Adult Sepsis Event definition. INTERVENTIONS: All patients received continuous infusion vasopressin as an adjunct to catecholamine vasopressors. MEASUREMENTS AND MAIN RESULTS: In total, 1,610 patients were included with a mean Acute Physiology and Chronic Health Evaluation III 109.0 ± 35.1 and Sequential Organ Failure Assessment 14.0 ± 3.5; 41% of patients survived the hospital admission. At the time of vasopressin initiation, patients had median (interquartile range) lactate concentration 3.9 mmol/L (2.3-7.2 mmol/L), norepinephrine-equivalent dose 25 µg/min (18-40 µg/min), and 5.3 hours (2.1-12.2 hr) elapsed since shock onset. The odds of in-hospital mortality increased 20.7% for every 10 µg/min increase in norepinephrine-equivalent dose up to 60 µg/min at the time of vasopressin initiation (adjusted odds ratio, 1.21 [95% CI, 1.09-1.34]), but no association was detected when the norepinephrine-equivalent dose exceeded 60 µg/min (adjusted odds ratio, 0.96 [95% CI, 0.84-1.10]). There was a significant interaction between timing of vasopressin initiation and lactate concentration (p = 0.02) for the association with in-hospital mortality. A linear association between increasing in-hospital mortality was detected for increasing lactate concentration at the time of vasopressin initiation, but no association was detected for time elapsed from shock onset. CONCLUSIONS: Higher norepinephrine-equivalent dose at vasopressin initiation and higher lactate concentration at vasopressin initiation were each associated higher in-hospital mortality in patients with septic shock who received vasopressin.

Augmented-Medication CardioPulmonary Resuscitation Trials in out-of-hospital cardiac arrest: a pilot randomized controlled trial.

BACKGROUND: Previously conducted physician-centered trials on the usefulness of vasopressin have yielded negative results; thus, patient-oriented trials have been warranted. We hypothesize that Augmented-Medication CardioPulmonary Resuscitation could be helpful for selected patients with out-of-hospital cardiac arrest (OHCA). METHODS: This is a double-blind, single-center, randomized, placebo-controlled trial conducted in the emergency department in a tertiary, university-affiliated hospital in Seoul, Korea. A total of 148 adults with non-traumatic OHCA who had initial diastolic blood pressure (DBP) < 20 mm Hg via invasive arterial monitoring during the early cardiac compression period were randomly assigned to two groups. Patients received a dose of 40 IU of vasopressin or placebo with initial epinephrine. The primary endpoint was a sustained return of spontaneous circulation. Secondary endpoints were survival discharge, and neurologic outcomes at discharge. RESULTS: Of the 180 included patients, 32 were excluded, and 148 were enrolled in the trial. A sustained return of spontaneous circulation was achieved by 27 patients (36.5%) in the vasopressin group and 24 patients (32.4%) in the control group (risk difference, 4.1%; P = .60). Survival discharge and good neurologic outcomes did not differ between groups. The trial group had significantly higher median DBPs during resuscitation than the control group (16.0 vs. 14.5 mm Hg, P < 0.01). There was no difference in end-tidal carbon dioxide, acidosis, and lactate levels at baseline, 10 min, and end-time. CONCLUSION: Among patients with refractory vasodilatory shock in OHCA, administration of vasopressin, compared with placebo, did not significantly increase the likelihood of return of spontaneous circulation.

Hemodynamic Response to Vasopressin Dosage of 0.03 Units/Min vs. 0.04 Units/Min in Patients With Septic Shock.

BACKGROUND: Arginine vasopressin (AVP) is suggested as an adjunct to norepinephrine in patients with septic shock. Guidelines recommend an AVP dosage up to 0.03 units/min, but 0.04 units/min is commonly used in practice based on initial studies. This study was designed to compare the incidence of hemodynamic response between initial fixed-dosage AVP 0.03 units/min and AVP 0.04 units/min. METHODS: This retrospective, multi-hospital health system, cohort study included adult patients with septic shock receiving AVP as an adjunct to catecholamine vasopressors. Patients were excluded if they received an initial dosage other than 0.03 units/min or 0.04 units/min, or AVP was titrated within the first 6 hours of therapy. The primary outcome was hemodynamic response, defined as a mean arterial pressure ≥65 mm Hg and a decrease in catecholamine dosage at 6 hours after AVP initiation. Inverse probability of treatment weighting (IPTW) based on the propensity score for initial AVP dosage receipt was utilized to estimate adjusted exposure effects. RESULTS: Of the 1536 patients included in the observed data, there was a nearly even split between initial AVP dosage of 0.03 units/min (n = 842 [54.8%]) and 0.04 units/min (n = 694 [45.2%]). Observed patients receiving AVP 0.03 units/min were more frequently treated at the main campus academic medical center (96.3% vs. 52.2%, p < 0.01) and in a medical intensive care unit (87.4% vs. 39.8%, p < 0.01). The IPTW analysis included 1379 patients with achievement of baseline covariate balance. There was no evidence for a difference between groups in the incidence of hemodynamic response (0.03 units/min 50.0% vs. 0.04 units/min 53.1%, adjusted relative risk 1.06 [95% CI 0.94, 1.20]). CONCLUSIONS: Initial AVP dosing varied by hospital and unit type. Although commonly used, an initial AVP dosage of 0.04 units/min was not associated with a higher incidence of early hemodynamic response to AVP in patients with septic shock.

Influence of Timing and Catecholamine Requirements on Vasopressin Responsiveness in Critically ill Patients with Septic Shock.

Introduction: Despite its widespread use, there is a paucity of data to guide the optimal use of arginine vasopressin (AVP) in critically ill patients with septic shock. Methods: This multicenter retrospective cohort study conducted in critically ill adults sought to evaluate the role of catecholamine requirements and timing on responsiveness to AVP. Responsiveness was defined as both a decrease in ≥ 50% of catecholamine requirements and no decrease in mean arterial pressure (MAP) at 4 hours post-AVP initiation. Primary outcomes of interest included the proportion of patients who started AVP within 4 hours after starting catecholamine therapy, as well as baseline norepinephrine (NE) equivalents (< 15, 15-39, or ≥ 40 mcg/min). Multivariate analyses and logistic regression were performed to identify other factors associated with AVP responsiveness. Results: There were 300 patients included in this study, with 74 patients being responders and 226 being non-responders. There was no significant difference in the number of patients who received AVP within 4 hours from catecholamine initiation between responders and non-responders (35% vs. 42%, P = 0.29). There were more patients in the non-responder group requiring ≥ 40 mcg/min of NE equivalents at AVP initiation (30% vs. 16%, P = 0.023). Stress dose steroid use was less common in responders (35% vs. 52%, P = 0.011), which was consistent with logistic regression analysis (OR 0.56, 95% 0.32-0.98, P = 0.044). Clinical outcomes between responders and non-responders were similar, apart from ICU (5.4% vs. 19.5%) and hospital (5.4% vs. 20.4%) mortality being lower in responders (P = 0.0032 and P = 0.0002, respectively). Conclusion: Shorter times to AVP initiation was not associated with responsiveness at 4 hours post-catecholamine initiation, although non-responders tended to require higher doses of NE equivalents at time of AVP initiation. Concomitant corticosteroids were associated with a lower likelihood of AVP responsiveness.

Vasopressin to Control Blood Loss during Hysterectomy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Minimizing intraoperative blood loss during hysterectomy is crucial to lessen associated perioperative morbidity. The aim of this investigation is to conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) that compared vasopressin versus normal saline in controlling intraoperative blood loss during hysterectomy. DATA SOURCES: We screened 5 major databases (PubMed, Scopus, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials) from inception till July 18, 2021. We used the following query search in all databases: (vasopressin OR arginine vasopressin OR argipressin OR antidiuretic hormone) AND (hysterectomy) AND (saline OR placebo OR control OR no treatment) AND (randomized OR randomised OR randomly). There was no language restriction during database screening. METHODS OF STUDY SELECTION: We considered all studies that met the following evidence-based criteria: (1) patients: individuals undergoing hysterectomy for any indication, (2) intervention: vasopressin, (3) comparator: normal saline, placebo, or no treatment, (4) outcomes: reliable extraction of any of our endpoints, and (5) study design: RCTs. We assessed risk of bias of included studies and pooled endpoints as mean difference (MD) or risk ratio (RR) with 95% confidence interval (CI). We performed statistical analysis using the Review Manager software, version 5.4.0. TABULATION, INTEGRATION, AND RESULTS: Seven RCTs with an overall low risk of bias met the inclusion criteria. This meta-analysis included a total of 455 patients; 232 and 223 patients were allocated to vasopressin and control group, respectively. The majority of RCTs were vaginal hysterectomy (n = 5), few abdominal hysterectomy, (n = 2) and no laparoscopic hysterectomy. The mean estimated intraoperative blood loss was significantly lower in favor of the vasopressin group compared with the control group (n = 6 RCTs, MD = -119.85 mL, 95% CI [-177.55, -62.14], p <.001). However, there was no significant difference between both groups regarding mean operating time, mean change in postoperative hemoglobin, mean hospital stay, rate of febrile morbidity, rate of pelvic infection, rate of perioperative blood transfusion, and rate of perioperative complications. CONCLUSION: Compared with normal saline, vasopressin significantly reduced the estimated blood loss during hysterectomy but did not change any clinically significant outcomes. In addition, vasopressin was safe and did not correlate with an increase in the rates of febrile morbidity or pelvic infection.