Serious Adverse Events after a Single Shot of Intrathecal Morphine: A Case Series and Systematic Review.

Background: The dose of intrathecal morphine is important because of its narrow therapeutic range. Due to a compounding error, pharmacy-compounded, ready-to-use syringes contained 1 mg ml-1 morphine instead of the intended 50 mcg ml-1. Six patients consequently received this twenty-fold dose. This study aims to describe the serious adverse events in these six patients and a systematic review is added to describe the characteristics of serious adverse events after intrathecal morphine. Methods: A retrospective case series described all six patients that received the erroneous morphine intrathecally for analgesia after laparoscopic segmental colonic resections. The patients' charts were reviewed for the occurrence, timing, duration and management of adverse events, the vital signs at the night after surgery, and length of hospital stay. A systematic review investigated characteristics of serious adverse events after intrathecal morphine in a perioperative setting. Results: Four patients had a serious adverse event, which was respiratory depression combined with somnolence (n = 3) and hypotension (n = 1). The review yielded 63 cases with serious adverse events, predominantly somnolence and/or respiratory depression. The onset occurred between 2 and 24 hours after injection. The severity of symptoms varied and life-threatening respiratory depression only occurred after a dose >900 mcg or when potentiating medication was used. Naloxone did not affect analgesia. No prolonged sequalae occurred. Conclusion: This study reveals that respiratory depression and somnolence are the predominant serious adverse events after intrathecal morphine in a perioperative setting and demonstrated a large variation in the presentation of symptoms.

Phenotypic variance in childhood coeliac disease and the HLA-DQ/DR dose effect.

OBJECTIVE: Coeliac disease (CD) is associated with HLA-DQ2 and DQ8. The clinical picture is variable and certain human leucocyte antigen (HLA) DQ/DR combinations have a higher relative risk (RR) for CD than others. Moreover, the HLA-DQ gene-dose effect has an impact on the strength of the gluten-specific T-cell response and thus may correlate with clinical presentation and severity of CD. The aim of this study was to determine the correlation between HLA-DQ/DR-based genotypes and the variation in phenotypes of the disease. MATERIAL AND METHODS: A total of 113 non-related Caucasian children clinically diagnosed with CD during the period 1980-2003 with a known HLA type were included in the study. Patients were divided into four categories according to amount of disease expression predisposing to HLA-DQ2 or HLA-DQ8 molecules and the known RR of their HLA-DR/DQ type for CD: high (DR3DQ2 homozygous and DR3DQ2/DR7DQ2), substantial (DR3DQ2/DR5DQ7 and DR5DQ7/DR7DQ2), moderate (DR3DQ2-DR4DQ8 and DR3DQ2/DR*DQ*) and low (DR7DQ2/DR*DQ*, DR4DQ8- DR*DQ* and DR*DQ*- DR*DQ*). The clinical data and HLA genotypes of these patients were compared. RESULTS: The 113 children were diagnosed with CD at a mean age of 4.6 years and boys were significantly older than girls when diagnosed (p=0.01). RR for having CD was highest for the high HLA-risk group (RR 8.1). With the exception of a greater frequency of abdominal distension and fewer non-gastrointestinal symptoms in the substantial HLA-risk group, there were no significant differences in clinical characteristics or degree of severity of the small-bowel histological findings between the children in the different HLA-risk groups. CONCLUSION: No correlation was found between disease severity and a double HLA-DQ2 gene dose.