Mortality, Morbidity, and Costs After Implementation of a Vasopressin Guideline in Medical Intensive Care Patients With Septic Shock: An Interrupted Time Series Analysis.

Background: Vasopressin decreases vasopressor requirements in patients with septic shock. However, the optimal norepinephrine dose for initiation or cessation of vasopressin is unclear. Objective: Analyze monthly intensive care unit (ICU) mortality rates 1 year preimplementation and postimplementation of a guideline suggesting a norepinephrine dose of 50 µg/min or more for initiation of vasopressin and early cessation of vasopressin. Methods: This retrospective quasi-experimental study included adult patients with septic shock admitted to the medical ICU of a tertiary care medical center over 2 years. Time periods were evaluated with interrupted time series analysis. Results: A total of 1148 patients were included: 573 patients preguideline and 575 patients postguideline. Group characteristics were well balanced at baseline, except patients postguideline had higher sequential organ failure assessment scores. Postguideline, fewer patients were initiated on vasopressin (305 [53.2%] vs 217 [37.7%], absolute difference -15.5% [95% CI -21.2% to -9.8%]), and the norepinephrine dose at vasopressin initiation was higher (median 25 [interquartile range 18, 40] µg/min vs 40 [22, 52] µg/min; median difference 15 [95% CI 11 to 19] µg/min; P < 0.01). After guideline implementation, there was no evidence for a difference in ICU mortality rate slope (slope change 0.07% [95% CI -0.8% to 1.0%] per month; P 0.87), but the vasoactive cost level decreased by US$183 (95% CI -US$327 to -US$39) per patient immediately after implementation. Conclusion and Relevance: Implementation of a guideline suggesting a high norepinephrine dose threshold for vasopressin initiation and early vasopressin cessation in patients with septic shock appears to be safe and may decrease vasoactive costs.

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.

[Assessment of different homeostatic methods used in laparoscopic intramural myomectomy].

OBJECTIVE: To explore the safe and effective method of hemostasis in laparoscopic hysteromyomectomy (LM). METHODS: Two hundred and eighty women with symptomatic uterine intramural fibroids undergoing LM were assigned to 4 groups, Group A undergoing fibroid pedicle ligation, Group B injected with 12 IU diluted vasopressin around the myoma, Group C injected with 20 IU oxytocin combined with pedicle ligation, and Group D injected with vasopressin combined with pedicle ligation. The operation time, amount of blood loss, operative complications, bowel deflation, post-operative hemoglobin dropping, and length of hospital stay were compared. RESULTS: The amounts of blood loss of Groups A and C were (171 +/- 146) ml and (184 +/- 140) ml, both significantly higher than those of Groups B and D [(115 +/- 70) ml and (106 +/- 73) ml, both P < 0.01]. The length of hospital stay of Group D was (2.9 +/- 0.5) d, significantly shorter than those of Groups A, B, and C [(3.1 +/- 0.7) d, (3.6 +/- 0.8) d, and (3.3 +/- 0.7) d, all P < 0.05]. The bowel deflation time of Group D was (20 +/- 6) h, significantly shorter than those of the Groups A, B, and C [(26 +/-) h, (25 +/- 7) h, and (25 +/- 8) h respectively, all P < 0.05]. The post-operative hemoglobin dropping of group D was (1.1 +/- 0.9) g/L, significantly less than those of Groups A, B, and C [(1.5 +/- 1.0), (1.4 +/- 0.8), and (1.2 +/- 0.7) g/L respectively, all P < 0.05]. CONCLUSIONS: Vasopressin (12 IU) injection around the myoma is a simple, effective, and safe homeostatic procedure during LM. Pedicle ligation can reduce advanced post-operative bleeding post-operation.

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.

New approaches to the treatment of sepsis.

The clinical spectrum of sepsis, severe sepsis, and septic shock is responsible for a growing number of deaths and excessive health care expenditures. Until recently, despite multiple clinical trials, no intervention provided a beneficial outcome in septic patients. Within the last 2 years, studies that involved drotrecogin alfa (activated), corticosteroid therapy, and early goal-directed therapy showed efficacy in those with severe sepsis and septic shock. These results have provided optimism for reducing sepsis-related mortality.

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.

Cost of treatment of bleeding esophageal varices.

We examined the cost of four methods of treatment of bleeding esophageal varices--medical treatment, sclerotherapy, variceal ligation operations, and portal systemic shunts--in 49 consecutive patients from 1977 to 1979, and correlated the two-year outcome with cost. We found that, despite bias imposed by selection, the cost per patient and cost per survivor at two years was lowest in patients who received sclerotherapy, even though they were more seriously ill than patients who received other treatments. Patients treated with sclerotherapy also had the lowest mortality during primary hospitalization and the lowest readmission rate during a two-year period.

The economic impact of acute variceal bleeding: cost-effectiveness implications for medical and surgical therapy.

The hospital costs and its respective components for 32 patients with acute variceal bleeding were determined. The average total cost for treating the 32 patients was $35,000. The cost for those patients who underwent elective surgery ($53,000) was approximately twofold that of the elective medical group. Nutritional and metabolic rehabilitation that prolonged hospitalization, reutilization of the intensive care unit, and perioperative blood requirements were the significant factors that increased the cost of treating the surgically treated patients. Derivation of the cost/benefit ratio, however, showed that the decreased rehospitalization rate of the surgically treated group and the apparent better "quality of life" almost offset the increased initial hospital costs for this group.