Dexmedetomidine impairs success of patient-controlled sedation in alcoholics during ERCP: a randomized, double-blind, placebo-controlled study

Background

There is a lack of studies about procedural sedation of alcoholics. Dexmedetomidine is recommended for procedural sedation and reported effective for alcohol withdrawal. We evaluated the suitability of dexmedetomidine for sedation of alcoholics during endoscopic retrograde cholangiopancreatography (ERCP).

Methods

Fifty patients with chronic alcoholism scheduled for elective ERCP were randomized 1:1 to receive dexmedetomidine (Dex group) (loading dose 1 μg kg^?1 over 10 min, followed by constant intravenous infusion 0.7 μg kg^?1 h^?1) or saline placebo (P group). Patient-controlled sedation with propofol–alfentanil was used by patients as a rescue method. Sedation was considered as successful if no intervention of an anesthesiologist was needed. Consumption of sedatives was registered, and sedation levels and vital signs were monitored.

Results

Dexmedetomidine alone was insufficient in all patients. The mean ± SD consumption of propofol was 159 ± 72 mg in the P group, and 116 ± 61 mg in the Dex group (p = 0.028). Sedation was successful in 19 of 25 (76 %) patients in the Dex group and in all patients in the P group (p = 0.022). The incidence of sedation adverse events did not differ between the groups. Dexmedetomidine was associated with delayed recovery.

Conclusions

Patient-controlled sedation with propofol and alfentanil but not dexmedetomidine can be recommended for sedation of alcoholics during ERCP.     

Outcome for self-expandable metal stents in malignant gastroduodenal obstruction: single-center experience with 104 patients

Background  

Malignant gastric outlet obstruction (GOO) leads to malnutrition and limits quality of life. Gastrojejunostomy has been the traditional treatment for GOO. Recently, the results of releasing duodenal obstruction with self-expandable metal stents (SEMS) have been encouraging.     

Clinical and biochemical characteristics and genotype-phenotype correlation in 143 Finnish and Russian patients with acute intermittent porphyria

Acute intermittent porphyria (AIP), resulting from a deficiency of porphobilinogen deaminase (PBGD) in heme biosynthesis, is genetically heterogeneous and manifests with variable penetrance. The clinical outcome, prognosis, and correlation between PBGD genotype and phenotype were investigated in 143 Finnish and Russian AIP patients with 10 mutations (33G-->T, 97delA, InsAlu333, R149X, R167W, R173W, R173Q, R225G, R225X, 1073delA). Thirty-eight percent of the patients had experienced 1 or more acute attacks during their lives. The proportion of symptomatic patients has decreased dramatically from 49% to 17% among patients diagnosed before and after 1980, respectively. Patients with the R167W and R225G mutations showed lower penetrance (19% and 11%, respectively) and recurrence rate (33% and 0%, respectively) than patients with other mutations (range, 36%-67% and 0%-66%, respectively). Moreover, urinary excretions of porphyrins and their precursors were significantly lower in these patients (porphobilinogen [PBG], 47 +/- 10 vs. 163 +/- 21 micromol/L, p < 0.001; uroporphyrin, 130 +/- 40 vs. 942 +/- 183 nmol/d, p < 0.001). Erythrocyte PBGD activity did not correlate with PBG excretion in remission or with the clinical severity of the disease. Mutations R167W and R225G resulted in milder biochemical abnormalities and clinical symptoms indicating a milder form of AIP in these patients. In all AIP patients, normal PBG excretion predicted freedom from acute attacks. The risk of symptoms was highest for female patients with markedly increased PBG excretion (>100 micromol/L). Proper counseling contributed to the prevention of subsequent attacks in 60% of previously symptomatic and in 95% of previously symptom-free patients.     

Centronuclear myopathies: genotype–phenotype correlation and frequency of defined genetic forms in an Italian cohort

Centronuclear myopathies (CNMs) are a group of clinically and genetically heterogeneous muscle disorders. To date, mutation in 7 different genes has been reported to cause CNMs but 30 % of cases still remain genetically undefined. Genetic investigations are often expensive and time consuming. Clinical and morphological clues are needed to facilitate genetic tests and to choose the best approach for genetic screening. We aimed to describe genotype–phenotype correlation in an Italian cohort of patients affected by CNMs, to define the relative frequencies of its defined genetic forms and to draw a diagnostic algorithm to address genetic investigations. We recruited patients with CNMs from all the Italian tertiary neuromuscular centers following clinical and histological criteria. All selected patients were screened for the four ‘canonical’ genes related to CNMs: MTM1, DNM2, RYR1 and BIN1. Pathogenetic mutations were found in 38 of the 54 screened patients (70 %), mostly in patients with congenital onset (25 of 30 patients, 83 %): 15 in MTM1, 6 in DNM2, 3 in RYR1 and one in TTN. Among the 13 patients with a childhood–adolescence onset, mutations were found in 6 patients (46 %), all in DNM2. In the group of the 11 patients with adult onset, mutations were identified in 7 patients (63 %), again in DNM2, confirming that variants in this gene are relatively more common in late-onset phenotypes. The present study provides the relative molecular frequency of centronuclear myopathy and of its genetically defined forms in Italy and also proposes a diagnostic algorithm to be used in clinical practice to address genetic investigations.