Propranolol and metoprolol: Two comparable drugs with very different post-mortem toxicological profiles.

Propranolol is a widely used beta-blocker mainly prescribed for the treatment of hypertension and other cardiac conditions. This medicine is also a frequent finding in drug screens, but little is known about its post-mortem toxicological profile. Our aim was to examine all post-mortem toxicology cases positive for propranolol in a three-year period, between 2016 and 2018 in Finland, and to compare these cases to those positive for metoprolol, another beta-blocker commonly used to treat cardiac diseases. There were 179 cases positive for propranolol and 416 for metoprolol in the study period. In the majority of propranolol cases (53%), the drug concentration in the blood was above the typical therapeutic range, but among the metoprolol cases this proportion was 18%. Propranolol was significantly more common than metoprolol in fatal poisonings, suicides and in cases with a history of drug abuse. Alcohol, benzodiazepines, antipsychotics and antidepressants were significantly more often detected in propranolol cases than in metoprolol cases. The deceased positive for propranolol were significantly younger than those positive for metoprolol. Cardiovascular diseases as the underlying cause of death were significantly more common among the metoprolol cases than among the propranolol cases. Our results showed significant differences between the propranolol group and the metoprolol group in post-mortem toxicology cases. The two drugs were used by two very different groups of people, with propranolol use being associated with psychiatric conditions.

Acetaminophen improves analgesia but does not reduce opioid requirement after major spine surgery in children and adolescents.

STUDY DESIGN: A randomized, placebo-controlled, double-blind study to evaluate the effect of intravenously (IV) administered acetaminophen on postoperative pain in children and adolescents undergoing surgery for idiopathic scoliosis or spondylolisthesis. OBJECTIVE: To evaluate effectiveness of IV-administered acetaminophen on postoperative analgesia, opioid consumption, and acetaminophen concentrations after major spine surgery in adolescents. SUMMARY OF BACKGROUND DATA: Scoliosis surgery is associated with severe postoperative pain, most commonly treated with IV-administered opioids. Nonsteroidal anti-inflammatory drugs (NSAIDs), as adjuvant to opioids, improve analgesia and reduce the need for opioids. However, by inhibiting cyclo-oxygenase enzymes peripherally, NSAIDs may inhibit bone healing. Acetaminophen, a centrally acting analgesic, does not have the adverse effects of NSAIDs and has improved analgesia in children after another orthopedic surgery. METHODS: In an institutional review board approved study, 36 American Society of Anesthesiology patient classification I to III patients of 10 to 18 years of age were analyzed. Acetaminophen 30 mg/kg, administered IV or 0.9% NaCl was administered at the end of scoliosis or spondylolisthesis surgery, and thereafter twice at 8-hour intervals. Timed blood samples for acetaminophen determination were taken between 0.25 and 20 hours after the first dose. All patients received standard propofol-remifentanil anesthesia. Pain scores (visual analogue scale [VAS], 0-10), opioid consumption, and adverse effects were recorded. RESULTS: In the surgical ward, 7 (39%) patients in the acetaminophen and 13 (72%) in the placebo group had a VAS pain score 6 or more (P < 0.05). There were fewer hours with VAS score 6 or more in the acetaminophen group compared with the placebo group (8.7% vs. 17.8% of the hours, P < 0.05). There was no difference in oxycodone consumption during the 24-hour follow-up between the 2 groups. CONCLUSION: IV-administered acetaminophen 90 mg/kg/day, adjuvant to oxycodone, did improve analgesia, but did not diminish oxycodone consumption during 24 hours after major spine surgery in children and adolescents. All acetaminophen concentrations were in nontoxic levels.

Comparing the effect of hydroxyethyl starch 130/0.4 with balanced crystalloid solution on mortality and kidney failure in patients with severe sepsis (6S--Scandinavian Starch for Severe Sepsis/Septic Shock trial): study protocol, design and rationale for a double-blinded, randomised clinical trial.

BACKGROUND: By tradition colloid solutions have been used to obtain fast circulatory stabilisation in shock, but high molecular weight hydroxyethyl starch (HES) may cause acute kidney failure in patients with severe sepsis. Now lower molecular weight HES 130/0.4 is the preferred colloid in Scandinavian intensive care units (ICUs) and 1st choice fluid for patients with severe sepsis. However, HES 130/0.4 is largely unstudied in patients with severe sepsis. METHODS/DESIGN: The 6S trial will randomize 800 patients with severe sepsis in 30 Scandinavian ICUs to masked fluid resuscitation using either 6% HES 130/0.4 in Ringer's acetate or Ringer's acetate alone. The composite endpoint of 90-day mortality or end-stage kidney failure is the primary outcome measure. The secondary outcome measures are severe bleeding or allergic reactions, organ failure, acute kidney failure, days alive without renal replacement therapy or ventilator support and 28-day and 1/2- and one-year mortality. The sample size will allow the detection of a 10% absolute difference between the two groups in the composite endpoint with a power of 80%. DISCUSSION: The 6S trial will provide important safety and efficacy data on the use of HES 130/0.4 in patients with severe sepsis. The effects on mortality, dialysis-dependency, time on ventilator, bleeding and markers of resuscitation, metabolism, kidney failure, and coagulation will be assessed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00962156.

Dexmedetomidine versus propofol/midazolam for long-term sedation during mechanical ventilation.

PURPOSE: To compare dexmedetomidine (DEX) with standard care (SC, either propofol or midazolam) for long-term sedation in terms of maintaining target sedation and length of intensive care unit (ICU) stay. METHODS: A pilot, phase III, double-blind multicenter study in randomized medical and surgical patients (n = 85) within the first 72 h of ICU stay with an expected ICU stay of >or=48 h and sedation need for >or=24 h after randomization. Patients were assigned to either DEX (