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A prospective, randomized trial was undertaken to compare the nutritional efficacy in surgical stress of a standard amino acid solution and two branched chain-enriched amino acid solutions: one enriched primarily with valine, the other with leucine. The study comprised 37 patients in the surgical intensive care unit who received isocaloric, isonitrogenous parenteral nutrition started within 24 hours of the onset of major operation, injury, or sepsis. Nitrogen retention was marginally but statistically significantly better on days 5, 7, and 10 in both groups of patients receiving the branched chain-enriched solutions, but differences in cumulative nitrogen balance were not statistically significant. Amino acid composition appeared to be important in that the group receiving the leucine-enriched solution appeared to maintain hepatic protein synthesis better (as manifest by higher short-turnover plasma protein concentrations) and required less exogenous insulin to maintain euglycemia. Improved outcome was not seen in the groups receiving the branched chain-enriched solutions.

The effect of indomethacin on protein degradation in skeletal muscle from septic rats was investigated. Sepsis was induced by cecal ligation and puncture (CLP). Control rats were sham-operated. Protein degradation rate was estimated by measuring release of tyrosine from incubated soleus (SOL) and extensor digitorum longus (EDL) muscles. Three experiments were performed. In the first experiment, indomethacin was administered subcutaneously (3 mg/kg) at the time of CLP and again after 3 hours. Control rats received corresponding volumes of solvent. Groups of rats were studied after 8 hours (early sepsis) or 16 hours (late sepsis). In the second experiment, the animals were pretreated 45 minutes before induction of sepsis with indomethacin (3 mg/kg) and again 3 hours after CLP and were studied during early sepsis. In the third experiment, indomethacin was added in vitro (3 microM) to incubated normal or septic muscle or to normal muscle incubated in the presence of plasma from septic animals, and release of prostaglandin E2 (PGE2) by incubated muscle was measured in addition to protein degradation. There was no mortality in early sepsis. Survival rate 16 hours after CLP was 8/16 (50%) in rats receiving control injections and 7/15 (47%) in indomethacin-treated rats (NS). Proteolytic rate in incubated EDL and SOL was increased by 20-25% during early sepsis and by 30-50% during late sepsis. The increased proteolytic rate was not affected by administration of indomethacin, neither in the first nor in the second experiment. When indomethacin was added in vitro, release of PGE2 by septic muscles and by normal muscles incubated in the presence of septic plasma was reduced by about 50%, but the increased proteolytic rate in these muscles was not affected. In normal muscle, neither release of PGE2 nor protein degradation was affected by indomethacin in vitro. The present results do not support a role for prostaglandins in the enhancement of muscle proteolysis during sepsis. Since neither survival rate nor protein breakdown was affected by indomethacin, recent suggestions to use this substance in the treatment of septic patients might be questioned.

Tunnelled silicone rubber right atrial catheters are commonly used to administer long-term total parenteral nutrition (TPN), cancer chemotherapeutic agents, and antimicrobial agents. The indwelling devices potentiate platelet-fibrin thrombi formation, providing a nidus for infection. Although many episodes of sepsis associated with thrombotic tunnelled catheters respond to antimicrobial therapy alone, a significant number require catheter removal. Evidence from case studies and small clinical trials suggests that fibrinolytic agents may increase the response rate and prevent removal of the device when combined with antimicrobial therapy. We present the first case reported of bacterial sepsis secondary to a thrombotic indwelling Hickman catheter for long-term TPN successfully treated with a combination of streptokinase and antibiotic therapies.

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The Washington State Death with Dignity (DWD) Act passed into law in November 2008 and allows terminally ill adults with a life expectancy of fewer than 6 months to requestlethaldosesofbarbituratemedicationstoendtheir lives. Participants have cited concerns about loss of autonomy,dignity,andabilitytoengageinactivitiesthatmake life enjoyable as reasons for participating in the program. 1,2 Since 2009, the number of DWD prescriptions dispensed in Washington State has steadily increased, and the majority of patients (approximately 75% with cancer diagnoses) to whom the medications are dispensed will ingest them. 1 The DWD program has generally been considered successful and patients have reported feeling grateful to have an option for physician-assisted death. 2 Today, however, patients and their families are raising new concerns about the high cost of DWD medication and the unaffordability of ending their lives in this way.We reviewed data on all DWD prescriptions written and dispensed at the Seattle Cancer Care Alliance, the outpatient oncology clinic for the Fred Hutchinson Cancer Research Center and the University of Washington. Since 2010,atotalof73DWDprescriptionshavebeendispensed to terminally ill patients with cancer. Consistent with broader prescribing patterns in Oregon and Washington, secobarbital (Seconal), an oral barbiturate, was the most commonly prescribed DWD medication (48%) (Table ). Oral pentobarbital was the next most commonly prescribed barbiturate, though prescriptions dropped sharply in 2014 after the manufacturer halted sales of the drug in response to its increasing use in state executions. Mean out-of-pocket cost for secobarbital increased steadily between 2010 ($387.52) and 2016 ($2878.09). Since DWD medicationsarenotconsideredtherapeutic,theyarerarely coveredbypublicorprivatehealthinsuranceplans,andpatients must bear the entire cost of the prescription. Due to the increased cost of secobarbital in 2015 and 2016, pharmacists at the Seattle Cancer Care Alliance referred 16 patients during this time to outside compounding pharmacies to receive a cocktail of phenobarbital, chloral hydrate, and morphine sulfate at a cost of $500.

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