Trends in Phenylephrine and Pseudoephedrine Sales in the US.

This study examines purchasing patterns regarding oral decongestants, concerns about their efficacy, and the need for timelier postmarket evaluation.

Rapid response to the alpha-1 adrenergic agent phenylephrine in the perioperative period is impacted by genomics and ancestry.

The emergence of genomic data in biobanks and health systems offers new ways to derive medically important phenotypes, including acute phenotypes occurring during inpatient clinical care. Here we study the genetic underpinnings of the rapid response to phenylephrine, an α1-adrenergic receptor agonist commonly used to treat hypotension during anesthesia and surgery. We quantified this response by extracting blood pressure (BP) measurements 5 min before and after the administration of phenylephrine. Based on this derived phenotype, we show that systematic differences exist between self-reported ancestry groups: European-Americans (EA; n = 1387) have a significantly higher systolic response to phenylephrine than African-Americans (AA; n = 1217) and Hispanic/Latinos (HA; n = 1713) (31.3% increase, p value < 6e-08 and 22.9% increase, p value < 5e-05 respectively), after adjusting for genetic ancestry, demographics, and relevant clinical covariates. We performed a genome-wide association study to investigate genetic factors underlying individual differences in this derived phenotype. We discovered genome-wide significant association signals in loci and genes previously associated with BP measured in ambulatory settings, and a general enrichment of association in these genes. Finally, we discovered two low frequency variants, present at ~1% in EAs and AAs, respectively, where patients carrying one copy of these variants show no phenylephrine response. This work demonstrates our ability to derive a quantitative phenotype suited for comparative statistics and genome-wide association studies from dense clinical and physiological measures captured for managing patients during surgery. We identify genetic variants underlying non response to phenylephrine, with implications for preemptive pharmacogenomic screening to improve safety during surgery.

Real-world opioid prescribing after cataract surgery among patients who received intracameral phenylephrine and ketorolac 1.0%/0.3.

OBJECTIVE: To examine opioid prescribing following cataract surgery among patients who did or did not receive Omidria (phenylephrine and ketorolac intraocular solution 1.0%/0.3%) referred to as "P/K". METHODS: The retrospective study compared adults over 65 without recent opioid use in the MarketScan databases who had a cataract-related surgical procedure between 1 January 2015 and 31 July 2019. Opioid prescription fills in the initial 2 and 7 days following surgery were compared between patients who did or did not receive P/K during surgery. RESULTS: We identified 218,672 older adults with cataract-related surgical procedures, of whom 5145 received P/K during surgery. Within 2 days of surgery, 0.50% of P/K patients and 0.68% of non-P/K patients received at least one opioid prescription. Pill counts in the first prescription post-surgery were lower for patients who received P/K than those who did not receive P/K (20 vs 45 respectively, p = .015). Findings were similar when a 7 day window was used. The reduction in opioids prescribed to patients who received P/K occurred despite the P/K-treated patients having a significantly higher incidence of preoperative comorbidities or risk factors for surgical complexity than patients who did not receive P/K (46.6% vs 31.3%, p < .001). CONCLUSIONS: Patients without recent opioid use who received P/K during cataract surgery, despite greater incidence of preoperative comorbidities and higher risk for surgical complexity, were prescribed fewer opioid pills following surgery than patients who did not receive P/K.

An enhanced recovery after surgery pathway for cesarean delivery decreases hospital stay and cost.

BACKGROUND: Enhanced recovery after surgery pathways provide a multidisciplinary, evidence-based approach to the care of surgical patients. They have been shown to decrease postoperative length of stay and cost in several surgical subspecialties, including gynecology, but have not been well-studied in obstetric patients who undergo cesarean delivery. OBJECTIVE: We sought to determine whether the implementation of an enhanced recovery after surgery pathway for cesarean delivery would decrease postoperative length of stay and postoperative direct cost compared with historic controls. STUDY DESIGN: We conducted a retrospective cohort study that compared postoperative length of stay and postoperative direct cost among women on the enhanced recovery after surgery cesarean delivery pathway in the first year of implementation (April 1, 2017, to March 31, 2018; n=531) compared with historic controls (March 1, 2016, to February 28, 2017; n=661). Literature review informed the development of a prototype enhanced recovery after surgery pathway for cesarean delivery based on best practices from previous enhanced recovery after surgery experience in obstetrics (if available) or from other surgical disciplines if there were no available data for obstetrics. When there was not relevant published evidence from obstetrics, the taskforce used clinical experience and expert opinion to develop the pathway. The enhanced recovery after surgery cesarean delivery pathway included preadmission patient education and preoperative, intrapartum, and postoperative elements. Some components reflected standard obstetric care, and others were specific to the enhanced recovery after surgery pathway. Women with pregestational diabetes mellitus who were receiving insulin therapy before pregnancy, women with preeclampsia with severe features, women with complex pain needs, and women with surgical complications were excluded from baseline and implementation groups. Enhanced recovery after surgery cesarean delivery pathway participation was determined by order set usage. Analysis was stratified for women who underwent planned (no labor; n=530) and unplanned (labor; n=662) cesarean delivery. Demographic and clinical characteristics, postoperative length of stay, postoperative direct cost, and readmission rates for the baseline and implementation groups were compared with the use of chi-square and t-tests. RESULTS: During the first year of implementation, 531 of 640 eligible women (83%) were included in the enhanced recovery after surgery cesarean delivery pathway. Body mass index was marginally higher in the baseline group for unplanned cesarean delivery (32.5±7.1 vs 31.4±6.7 kg/m2; P=.04). Otherwise there were no significant differences in demographic or maternal clinical characteristics between baseline or implementation groups overall or for planned or unplanned cesarean delivery. Compared with baseline, implementation of the enhanced recovery after surgery cesarean delivery pathway resulted in a significant decrease in postoperative length of stay by 7.8% or 4.86 hours overall (P<.001) and for both planned (P=.001) and unplanned (P=.002) cesarean delivery. Total postoperative direct costs decreased by 8.4% or $642.85 per patient overall (P<.001) and for both planned (P<.001) and unplanned (P<.001) cesarean delivery. There were no significant differences in readmission rates. CONCLUSION: Implementation of an enhanced recovery after surgery pathway for women who had planned or unplanned cesarean delivery was associated with significantly decreased postoperative length of stay and significant direct cost-savings per patient, without an increase in hospital readmissions. Given that cesarean delivery is 1 of the most common surgical procedures performed in the United States, positively impacting postoperative length of stay and direct cost for women who undergo cesarean delivery could have significant healthcare cost-savings.

Spinal-induced hypotension: Incidence, mechanisms, prophylaxis, and management: Summarizing 20 years of research.

Hypotension commonly occurs in parturients undergoing cesarean delivery under spinal anesthesia. This leads to maternal and neonatal adverse outcomes, including maternal nausea and vomiting and fetal acidosis, and might even lead to cardiovascular collapse if not treated. Arterial dilatation and reduction in systemic vascular resistance are the major contributors to spinal-induced hypotension. Therefore, strategies aimed at expanding the intravascular volume with fluid loading or increasing venous return with lower extremities mechanical compression and lateral tilt have had limited effectiveness in the management of spinal-induced hypotension. Vasopressors are therefore the mainstay for the prophylaxis and treatment of spinal-induced hypotension. Phenylephrine is associated with improved neonatal acid-base status and a lower risk of maternal nausea and vomiting compared with ephedrine and is now considered the vasopressor of choice in obstetric patients. This review discusses the various strategies for managing spinal-induced hypotension with a particular emphasis on the optimal use of vasopressors.

Assessment of an updated double-vasopressor automated system using Nexfin for the maintenance of haemodynamic stability to improve peri-operative outcome during spinal anaesthesia for caesarean section.

Hypotension occurs commonly during spinal anaesthesia for caesarean section, associated with maternal and fetal adverse effects. We developed a double-vasopressor automated system with a two-step algorithm and continuous non-invasive haemodynamic monitoring using the Nexfin device. The system delivered 25 µg phenylephrine every 30 s when systolic blood pressure was between 90% and 100% of baseline, or 2 mg ephedrine at this blood pressure range and heart rate < 60 beats.min(-1) ; and 50 µg phenylephrine or 4 mg ephedrine when systolic blood pressure was < 90% of baseline with the same heart rate criterion. Fifty-seven women received standardised spinal anaesthesia. Twenty-seven (47.4%) had at least one reading of hypotension defined as systolic blood pressure < 80% baseline. Systolic blood pressure was within 20% of the baseline in a mean (SD) of 79.8 (20.9)% of measurements. Fifty-three (93.0%) women required phenylephrine before delivery while 10 (17.5%) required ephedrine. Six women (10.5%) experienced nausea and three (5.3%) vomited. The system was able to achieve a low incidence of maternal hypotension with good maternal and fetal outcomes.

Risk of contamination of lidocaine hydrochloride and phenylephrine hydrochloride topical solution: in vivo and in vitro analyses.

OBJECTIVE: To investigate the risk of contamination of lidocaine hydrochloride 5 per cent weight/volume and phenylephrine hydrochloride 0.5 per cent weight/volume topical solution, both in patients (in vivo) and in the laboratory setting (in vitro). METHODS: This paper reports a prospective study involving 10 samples of the lidocaine hydrochloride and phenylephrine hydrochloride topical anaesthetic spray. The samples were assessed for microbiological contamination after a single use on patients in a controlled laboratory environment. Additional samples were assessed for baseline contamination and later assessed for contamination in an in vitro setting. RESULTS: In the in vivo setting, 2 of the 10 samples were positive for cultures from both the pump and the bottles. However, in the in vitro setting, the pump and the contents of the bottles were contaminated after a single use when the sterile solution was sprayed from distances of 1 and 2 cm. CONCLUSION: The lidocaine hydrochloride and phenylephrine hydrochloride topical solution assembly was contaminated in both in vivo and in vitro settings after a single use.

Controlling hypertension and hypotension immediately post stroke (CHHIPS)--a randomised controlled trial.

OBJECTIVES: To assess the effects of acute pressor and depressor blood pressure (BP) manipulation on 2-week death and dependency following acute stroke and investigate the safety and efficacy of such treatments. DESIGN: A multicentre, prospective, randomised, double-blind, placebo-controlled titrated-dose trial. SETTING: Five hospitals in England. PARTICIPANTS: Patients over 18 years admitted to hospital with a clinical diagnosis of suspected stroke and either (1) symptom onset < 36 hours and hypertension, defined as systolic BP (SBP) < 160 mmHg (depressor arm), or (2) symptom onset < 12 hours and hypotension, defined as SBP < or = 140 mmHg (pressor arm). INTERVENTIONS: Patients were allocated to either the pressor or the depressor arm depending on blood pressure at randomisation. The ratio of allocation to active intervention versus matched placebo was 2:1 for the depressor arm and 1:1 for the pressor arm. MAIN OUTCOME MEASURES: The primary end point was death and dependency at 2 weeks, with dependency defined as a modified Rankin score < 3. Secondary end points were the safety of acute pressor (0-12 hours post stroke) and depressor (0-36 hours post stroke) BP manipulation in stroke patients; whether effects of BP reduction are influenced by stroke type (ischaemic versus haemorrhagic); whether alternative routes for administration of antihypertensive therapy (including sublingual and intravenous) are effective in dysphagic stroke patients; whether effects of BP manipulation are influenced by the time to treatment; and the short- and medium-term cost-effectiveness of such therapy in the acute post-stroke period on subsequent disability or death. RESULTS: 180 patients were recruited over the 36-month trial period, 179 in the depressor arm and one in the pressor arm (who received placebo). No significant difference was found in death or dependency at 2 weeks between those receiving active depressor treatment with lisinopril or labetalol and those receiving placebo, although numbers recruited to the trial were lower than projected. Active treatment was not associated with an increase in early neurological deterioration despite significantly greater reductions in BP at 24 hours and 2 weeks with active therapy compared with placebo. Active treatment was generally well tolerated and treatment discontinuation rates were similar in active and placebo groups. Survival analysis showed that the active treatment group had a lower mortality at 3 months than the placebo group (p = 0.05). The pressor arm was closed early because of problems with recruitment, so no conclusions can be drawn regarding this therapy. CONCLUSIONS: Oral and sublingual lisinopril and oral and intravenous labetalol are effective BP-lowering agents in acute cerebral infarction and haemorrhage and do not increase the likelihood of early neurological deterioration. The study was not sufficiently powered to detect a difference in disability or death at 2 weeks. However, the 3-month difference in mortality in favour of active treatment is of interest, although care must be taken in interpretation of the results. Further work is needed to confirm this and to assess whether there are differences in the effectiveness of labetalol compared with lisinopril in terms of reducing death or dependency after acute stroke, and whether the introduction of treatment post stroke earlier than was achieved here would be of greater benefit.

Comparison of surgical versus medical treatment of nephrosplenic entrapment of the large colon in horses: 19 cases (1992-2002).

OBJECTIVE: To compare the outcome of horses with nephrosplenic entrapment of the large colon (NSELC) treated surgically or medically by rolling, administration of phenylephrine hydrochloride (or both), and exercise. DESIGN: Retrospective study. ANIMALS: 11 medically treated horses and 8 surgically treated horses with NSELC. PROCEDURE: Medical records of horses with nephrosplenic entrapment between 1992 and 2002 were reviewed. Medically treated horses were included if diagnosis and outcome of treatment of nephrosplenic entrapment were confirmed via transrectal examination and ultrasonographic examination. Surgically treated horses were included if the diagnosis was confirmed by exploratory laparotomy. Horses in which the large colon was entrapped between the spleen and body wall were not included. RESULTS: Significant differences in mean age, heart rate, and duration of colic prior to treatment were not detected between horses treated surgically or medically. Ten medically treated horses recovered without complications, and 1 died. In the surgically treated group, 6 of 8 horses recovered without complications and 2 died. Mortality rate did not differ between treatments. Duration of hospitalization for medically treated horses was significantly shorter and the cost significantly less than for surgically treated horses. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that medical treatment of horses with NSELC via administration of phenylephrine hydro-chloride, rolling during general anesthesia, or both appears to be as effective as and less expensive than surgical treatment.

The incidence and management of priapism in Western Australia: a 16 year audit.

The objective of the study was to conduct a retrospective audit of patients who presented with priapism in Western Australia during the years 1985-2000. We searched the records of the teaching hospitals in metropolitan Perth and those of the Keogh Institute for Medical Research for the diagnostic code for priapism. A total of 82 episodes of priapism in 63 patients occurred over this 16 year period. In all, 62 episodes occurred after intracavernosal injections (ICI) and 20 were due to other causes. Treatment of priapism included simple aspiration of blood, intracavernosal injection of alpha-adrenergic agents and surgical shunt procedures. Priapism occurring outside the setting of ICI was more likely to require surgery; seven of 20 episodes. After ICI therapy, eight of 62 episodes required shunts. The use of prostaglandin E1 as the drug of choice in ICI therapy in 1989 led to a fall in the incidence of ICI-induced priapism. Priapism is a major side effect of ICI therapy and an uncommon, although important, side effect of other conditions. The incidence of priapism has fallen with the introduction of prostaglandin E1 monotherapy as the favoured drug for ICI therapy of erectile failure.

A multicenter, randomized, blind comparison of amrinone with milrinone after elective cardiac surgery.

UNLABELLED: Amrinone and milrinone are phosphodiesterase inhibitors with positive inotropic effects useful for the treatment of ventricular dysfunction after cardiac surgery. Forty-four patients undergoing elective cardiac surgery at four centers received either amrinone (n = 22) or milrinone (n = 22) in a randomized, blind fashion. Immediately after separation from cardiopulmonary bypass (CPB), two bolus doses of either amrinone 0.75 mg/kg or milrinone 25 microg/kg were administered over 30 s, separated by 5 min. Hemodynamic measurements were recorded before each dose and at the end of the 10-min study. Both amrinone and milrinone increased the cardiac index (48% vs 52%, P = not significant [NS] for amrinone and milrinone, respectively). There was a small increase in mean arterial pressure (MAP) after amrinone administration (from 68 +/- 3 to 72 +/- 3 mm Hg at 10 min, P < 0.05) with no significant change in MAP after milrinone administration. Central venous pressure was significantly higher in the amrinone group at baseline and 5 min (12 vs 10 mm Hg and 11 vs 10 mm Hg, respectively; P < 0.05). Systemic and pulmonary vascular resistances decreased significantly and to a similar extent after either amrinone or milrinone administration. Phenylephrine was required in 11 of 22 patients receiving amrinone and in 11 of 22 patients receiving milrinone to maintain arterial blood pressure. The proportion of patients requiring an intravascular volume infusion (15 of 22 vs 17 of 22, P = NS) and the total fluid volume infused were similar (402 +/- 57 vs 350 +/- 49 mL, P = NS for amrinone and milrinone, respectively). Amrinone and milrinone seem to have similar hemodynamic effects after CPB, with the exception of blood pressure, although the need for vasopressor support of blood pressure did not differ. Selection between these two drugs may include nonhemodynamic considerations such as cost. IMPLICATIONS: Amrinone and milrinone are drugs that improve cardiac contraction. Their effects have never been directly compared in patients. We found that amrinone and milrinone produced similar hemodynamic effects in adult patients undergoing cardiac surgery. Choice between the two drugs can be based on nonhemodynamic considerations such as cost.

Incidence and simple management of priapism following dynamic infusion cavernosometry-cavernosography.

Of 239 patients with erectile dysfunction (aged 36 to 70 years) who were evaluated with dynamic infusion cavernosometry-cavernosography, 32 (13.4%) developed priapism after the procedure and were successfully managed with immediate intracorporal injection of phenylephrine. No single risk factor for the development of priapism was identified in this group. Early pharmacologic intervention for priapism induced by dynamic infusion cavernosometry-cavernosography is a simple, safe, and time-saving measure to achieve detumescence and prevent potential sequelae such as corporal ischemia or fibrosis.