Delayed vasopressor initiation is associated with increased mortality in patients with septic shock.

PURPOSE: Mortality rate for septic shock, despite advancements in knowledge and treatment, remains high. Treatment includes administration of broad-spectrum antibiotics and stabilization of the mean arterial pressure (MAP) with intravenous fluid resuscitation. Fluid-refractory shock warrants vasopressor initiation. There is a paucity of evidence regarding the timing of vasopressor initiation and its effect on patient outcomes. MATERIALS AND METHODS: This retrospective, single-centered, cohort study included patients with septic shock from January 2017 to July 2017. Time from initial hypotension to vasopressor initiation was measured for each patient. The primary outcome was 30-day mortality. RESULTS: Of 530 patients screened,119 patients were included. There were no differences in baseline patient characteristics. Thirty-day mortality was higher in patients who received vasopressors after 6 h (51.1% vs 25%, p < .01). Patients who received vasopressors within the first 6 h had more vasopressor-free hours at 72 h (34.5 h vs 13.1, p = .03) and shorter time to MAP of 65 mmHg (1.5 h vs 3.0, p < .01). CONCLUSION: Vasopressor initiation after 6 h from shock recognition is associated with a significant increase in 30-day mortality. Vasopressor administration within 6 h was associated with shorter time to achievement of MAP goals and higher vasopressor-free hours within the first 72 h.

Cost-effectiveness of second-line vasopressors for the treatment of septic shock.

PURPOSE: To determine the cost-effectiveness of escalating doses of norepinephrine or norepinephrine plus the adjunctive use of vasopressin or angiotensin II as a second-line vasopressor for septic shock. MATERIALS AND METHODS: Decision tree analysis was performed to compare costs and outcomes associated with norepinephrine monotherapy or the two adjunctive second-line vasopressors. Short- and long-term outcomes modeled included ICU survival and lifetime quality-adjusted-life-years (QALY) gained. Costs were modeled from a payer's perspective, with a willingness-to-pay threshold set at $100,000/unit gained. One-way (tornado diagrams) and probabilistic sensitivity analyses were performed. RESULTS: Adjunctive vasopressin was the most cost-effective therapy, and dominated both norepinephrine monotherapy and adjunctive angiotensin II by producing higher ICU survival at less cost. For the lifetime horizon, while norepinephrine monotherapy was least expensive, adjunctive vasopressin was the most cost-effective with an incremental cost-effectiveness ratio of $19,762 / QALY gained. Although adjunctive angiotensin II produced more QALYs compared to norepinephrine monotherapy, it was dominated in the long-term evaluation by second-line vasopressin. Sensitivity analyses demonstrated model robustness and medication costs were not significant drivers of model results. CONCLUSIONS: Vasopressin is the most cost-effective second-line vasopressor in both the short- and long-term evaluations. Vasopressor price is a minor contributor to overall cost.

Hyperinflation of Vasopressors (Vasopressin, Norepinephrine, Ephedrine, etc).

PURPOSE: Hyperinflation refers to the increasing cost of drugs which occurs due to continued drug shortages and rebranding. Hyperinflation has significant implications in increasing overall healthcare costs with reduced reimbursement, increased patient acuity, and an aging population, but published strategies to reduce costs and minimize waste are limited. OBJECTIVE: To describe the hyperinflation and cost mitigation strategies of three vasopressor medications, vasopressin, epinephrine, and ephedrine. CONCLUSION: The steep increase in medications is expected to continue, and mitigation strategies to reduce waste and select the most cost effective therapy to offset the price increase is crucial for healthcare systems.

US Food and Drug Administration Disruption of Generic Drug Market Increases Hospital Costs.

BACKGROUND: The purpose of the US Food and Drug Administration's Marketed Unapproved Drugs Initiative is to decrease marketing of older unapproved medications. The administration has recently extended its rulings by including sterile injectable drugs administered in the inpatient environment. The impact of this initiative on the inpatient environment has been minimally studied. METHODS: Consecutive retrospective purchase data of vasopressin for injection (vasopressin) and neostigmine methylsulfate for injection (neostigmine) from 720 hospitals and 746 hospitals, respectively, were included. Purchases occurred from January 1, 2010 to December 31, 2016. The average noncontract drug price was calculated and compared to the purchase data during the impact of the initiative. Comparison was made of hospital purchases made before and after the initiative. The year 2014 was considered a washout transition year due to the large amounts of discontinued unapproved formulations that were still available and purchased by hospitals. The analysis was completed using a matched paired t test. RESULTS: The noncontract price for vasopressin increased from $12.83 per vial to $158.83 per vial (1138% increase) and for neostigmine from $27.74 per vial to $175.14 per vial (531% increase) across the pre- and postinitiative intervals; however, purchase volumes after the price increases were not found to have a statistically significant difference compared to purchases before the price increases (P = .98 and P = .4, respectively). CONCLUSIONS: Health systems have experienced a significant cost increase of vasopressin and neostigmine and are absorbing price increases for these older, generic sterile injectable drugs.

The safety and efficacy of the use of vasopressin in sepsis and septic shock.

Sepsis remains a significant problem and cause of morbidity and mortality in intensive care. Vasopressin infusions are currently used as rescue therapy for the treatment of vasodilatory, catecholamine-resistant septic shock. At present, there are no large randomised, controlled trials in the literature investigating vasopressin in this role, although two such studies are currently ongoing in Canada. This review outlines the pathophysiology of sepsis and that of vasopressin in sepsis and reviews the available evidence for the use of vasopressin in sepsis and septic shock. A review of the safety data for vasopressin in this indication is included. Recommendations for the use of vasopressin in septic shock, along with suggestions for the direction of further work in the field are presented.

Vasoconstrictors in the management of bleeding from oesophageal varices. A clinico-economic appraisal in the UK.

BACKGROUND: Bleeding from oesophageal varices is an uncommon but potentially fatal condition that often leads to expensive hospitalizations in intensive care or high-dependency units. METHODS: To assess the clinical and economic impact of this condition, we have devised a management plan illustrating current clinical practice in the UK. RESULTS: Approximately 6.1 million pounds of NHS resources are devoted to the treatment of 3000 acute hospital admissions for variceal bleeding every year. Vasoconstrictors like vasopressin may save approximately 36 lives per annum for an additional 145 thousand pounds. However, current clinical practice requires vasopressin to be concurrently administered with intravenous glyceryl trinitrate, increasing overall costs by 582 thousand pounds to a total of 6.7 million pounds. The additional cost for each extra life saved is estimated at 16,180 pounds. CONCLUSION: The efficacy of current vasoconstrictors requires further confirmation. In particular, new agents like octreotide (Sandostatin) should be carefully assessed to determine their potential clinical and economic benefits.