Background Delirium and pain are common and serious postoperative complications. Subanaesthetic ketamine is often administered intraoperatively for postoperative analgesia and to spare postoperative opioids. Some evidence also suggests that ketamine prevents delirium. The primary purpose of this trial was to evaluate the effectiveness of ketamine in preventing postoperative delirium in older adults after major surgery. Secondary outcomes, viewed as strongly related to delirium, were postoperative pain and opioid consumption. Methods This was a multicentre, international, randomised trial that enrolled adults older than 60 undergoing major cardiac and noncardiac surgery under general anaesthesia. Participants were enrolled prior to surgery and gave written informed consent. We used a computer-generated randomisation sequence. Patients at study sites were randomised to one of three study groups in blocks of 15 to receive intraoperative administration of (i) placebo (intravenous normal saline), (ii) low dose ketamine (0.5 mg/kg) or (iii) high dose ketamine (1 mg/kg). Study drug was administered following induction of anaesthesia, prior to surgical incision. Participants, clinicians, and investigators were all masked to group assignment. Delirium and pain were assessed twice daily in the first three postoperative days using the Confusion Assessment Method and Visual Analog Scale, respectively. Postoperative opioid use was recorded, and hallucinations and nightmares were assessed. Analyses were performed by intention-to-treat and adverse events were evaluated. The Prevention of Delirium and Complications Associated with Surgical Treatments [PODCAST] trial is registered in clinicaltrials.gov; NCT01690988 Findings Between February 6, 2014 and June 26, 2016, 1360 patients assessed and 672 were randomised, with 222 in the placebo group, 227 in the low dose ketamine group, and 223 in the high dose ketamine group. There was no difference in postoperative delirium incidence between those in the combined ketamine groups and those who received placebo (19.45% vs. 19.82%, respectively; absolute difference, 0.36%; 95% CI, −6.07% to 7.38%; p=0.92). There were no significant differences among the three groups in maximum pain scores (p=0.88) or median opioid consumption (p=0.47) over time. There were more postoperative hallucinations (p=0.01) and nightmares (p=0.03) with escalating doses of ketamine. Adverse events (cardiovascular, renal, infectious, gastrointestinal, bleeding), whether viewed individually (P value for each >0.40) or collectively (82/222 [36.9%] in placebo group, 90/227 [39.6%] in low dose ketamine group, 91/223 in high dose ketamine group [40.8%]; P=0.69), did not differ significantly across the three groups. Interpretation The administration of a single subanaesthetic dose of ketamine to older adults during major surgery did not show evidence of reducing postoperative delirium, pain, or opioid consumption, and might cause harm by inducing negative experiences. Given current evidence and guidelines related...
A double-blind controlled trial of thyrotropin releasing hormone (TRH) 150 mg IM daily in 30 patients with amyotrophic lateral sclerosis is reported. The drug/placebo was administered for 2 months, followed by a 2-month "wash-out". Evaluation of strength, functional ability, and respiratory functions was performed. A temporary increase in the strength of some muscles was detected following the administration of TRH, but no change in functional performance was noted. Neither the patients nor the investigators believed the effects were of any marked clinical significance. The course of the illness was not altered.
Objective: This article reports a case of secondary hypothyroidism occurring during the withdrawal of thyroid hormone replacement in a patient with thyroid cancer that led to the discovery of simultaneous panhypopituitarism and hyperprolactinemia that were caused by an internal carotid artery aneurysm. The discovery of the secondary hypothyroidism necessitated further pituitary hormone analysis and medical imaging to identify the precise pathologic etiology. Methods: The methods used included the evaluation of selected thyroid and pituitary hormone concentrations and subsequent pituitary magnetic resonance imaging. Results: An 86-year-old African-American female with a history of thyroid cancer exhibited a suppressed serum thyroid-stimulating hormone concentration that failed to increase during progressive lowering of her thyroxine dosage despite it causing a simultaneous subnormal free thyroxine concentration. Laboratory findings indicated secondary hypothyroidism and subsequently panhypopituitarism and hyperprolactinemia. Pituitary magnetic resonance imaging revealed the presence of a large carotid aneurysm that had invaded the sella turcica. Additional hormone analyses revealed elevated prolactin, low gonad
Objective: The objective of this publication is to report a case of secondary hypogonadism in a patient with diminished prostate-specific antigen (PSA) levels who was ultimately diagnosed with a pituitary macroadenoma. Methods: The methods used to collect our data include pituitary magnetic resonance imaging and summarization of thyroid and pituitary data, as well as documentation of PSA and testosterone levels. Results: A 64-year-old, white male with benign prostatic hyperplasia and prostatic intraepithelial neoplasia was found to have low testosterone levels and decreased sexual drive. The patient showed diminution of PSA levels (from 6.9 ng/dL to <0.05 ng/dL), which led us to suspect low testosterone levels. Further testing revealed progressive decrease in testosterone over a 5-year period to a nadir of <2.5 ng/dL. Additional lab data showed panhypopituitarism, indicating a secondary cause for the hypogonadism. These laboratory findings led to a pituitary magnetic resonance imaging study revealing a solid, cystic macroadenoma occupying the sella turcica and the left cavernous sinus with suprasellar extension. Conclusion: A spontaneous decrease in PSA levels indicates a need for further hormonal workup. If low testosterone levels are found concurrently, this may indicate a primary or secondary cause, for which a comprehensive evaluation of the pituitary-hypothalamic-testicular axis is warranted.
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