Mu-opioid receptor (A118G) single-nucleotide polymorphism affects alfentanil requirements for extracorporeal shock wave lithotripsy: a pharmacokinetic-pharmacodynamic study.

BACKGROUND: There are diverse reports concerning the single-nucleotide polymorphism (SNP) A118G in the gene coding for the mu-opioid receptor. This study assessed pharmacokinetic-pharmacodynamic relationships in patients with acute pain (water-immersed extracorporeal shock wave lithotripsy). METHODS: Ninety-nine patients (ASA I-II, age 18-70) were assessed in this prospective observational study. Blinding was achieved by determining genotype only after the procedure. I.V. alfentanil was administered by patient-controlled administration (loading dose, 10 microg kg(-1); continuous infusion, 20 microg kg(-1) h(-1); bolus, 3 microg kg(-1); lockout time, 1 min); no other analgesic or sedating medication was used. RESULTS: The allelic frequency was 15.2% in our population. The G118 SNP (AG/GG) was associated with a 27% increase in plasma alfentanil concentration (P=0.034), a 54% increase in alfentanil dose (P=0.009), a 47% increase in dose per kg body weight (P=0.004), a 55% increase in dose per kg corrected for stimulus intensity (P=0.002), a 112% increase in the numbers of attempted boluses (P=0.015), a 79% increase in the numbers of successful boluses (P=0.013), and a 153% increase in the numbers of failed boluses (P=0.042). Despite the increased alfentanil self-administration, the G118 SNP was associated with a 52% increase in verbal analogue pain scores over the same period of time (P=0.047). CONCLUSIONS: We demonstrated increased opioid requirement for alfentanil in patients with the G118 SNP, who self-administered a higher dose, achieved higher plasma concentration, and yet complained of more severe pain. This observation suggests that G118 SNP impairs the analgesic response to opioids.

Pulse oximeter perfusion index as an early indicator of sympathectomy after epidural anesthesia.

BACKGROUND: The pulse oximeter perfusion index (PI) has been used to indicate sympathectomy-induced vasodilatation. We hypothesized that pulse oximeter PI provides an earlier and clearer indication of sympathectomy following epidural anesthesia than skin temperature and arterial pressure. METHODS: Forty patients received lumbar epidural catheters. Patients were randomized to receive either 10 ml 0.5% bupivacaine or 10 ml 0.25% bupivacaine. PI in the toe, mean arterial pressure (MAP) and toe temperature were all assessed at baseline and at 5, 10 and 20 min following epidural anesthesia. The effect of epidural anesthesia over time was assessed by repeated measures analysis of variance. Additionally, we defined clinically evident sympathectomy criteria (a 100% increase in the PI, a 15% decrease in MAP and a 1 degrees C increase in toe temperature). The numbers of patients demonstrating these changes for each test were compared using the McNemar test for each time point. RESULTS: Twenty-nine subjects had photoplethysmography signals that met a priori signal quality criteria for analysis. By 20 min, PI increased by 326%, compared with a 10% decrease and a 3% increase in MAP and toe temperature, respectively. For PI 15/29, 26/29 and 29/29 of the subjects met the sympathectomy criteria at 5, 10 and 20 min, respectively, compared with 4/29, 6/29 and 18/29 for MAP changes and 3/29, 8/29 and 14/29 for toe temperature changes. CONCLUSIONS: PI was an earlier, clearer and more sensitive indicator of the development of epidural-induced sympathectomy than either skin temperature or MAP.

A randomized controlled trial using patient-controlled epidural analgesia with 0.25% versus 0.0625% bupivacaine in nulliparous labor: effect on analgesia requirement and maternal satisfaction.

BACKGROUND: The effect of epidural local anesthetic concentration on analgesic action is still the subject of debate. This study compared the effect of a four-fold change in concentration of bupivacaine for epidural analgesia in labor. METHODS: Nulliparous women in early active labor were recruited. All women received analgesic drugs via a lumbar epidural catheter, and all received fentanyl 1 microg/kg with the epidural induction dose and no further opioids throughout the study. Patients were randomized to receive either a 5-mL bolus followed by a 5-mL/h infusion of concentrated (0.25%) bupivacaine or a 20-mL bolus followed by a 20-mL/h infusion of dilute (0.0625%) bupivacaine. Patient-controlled epidural analgesia of the study solution was then used to assess additional analgesia requirements. Analgesic requirement, maternal satisfaction and obstetric outcome were compared. RESULTS: For subjects receiving 0.25% bupivacaine, the median total dose of drug administered was greater (117 vs. 90 mg, P=0.0008), and the mean maternal satisfaction score was less (82 vs. 93, P=0.04) than with the 0.0625% solution. CONCLUSIONS: Larger volumes of more dilute solutions may result in dose sparing and provide more effective labor analgesia. This study supports the continued trend towards dilute local anesthetic mixtures for labor epidural analgesia.

Predictors of mortality in hospitalized patients with secondary upper gastrointestinal haemorrhage.

OBJECTIVES: To identify clinical, laboratory and endoscopic features of prognostic implication in patients who suffer an upper gastrointestinal haemorrhage whilst hospitalized for other causes. DESIGN/SETTING: A prospective longitudinal study of 125 consecutive cases (89 males, 36 females) seen during 1988-1991 in a tertiary care university hospital. MAIN OUTCOME MEASURES: The crude and adjusted relative risk of mortality associated with each of the various clinical, laboratory and endoscopic variables. RESULTS: The rates of endoscopic haemostasis, persistent or recurrent bleeding and surgery to control bleeding were 48, 37 and 12%, respectively; the overall mortality was 28%. A significantly increased risk of mortality was associated with shock prior to onset of bleeding, sepsis, renal failure, cirrhosis, encephalopathy, presence of red blood in the nasogastric aspirate or per rectum, thrombocytopenia, hypoalbuminaemia, elevation of serum bilirubin, aminotransferases or urea levels, endoscopic evidence of active bleeding, the application of endoscopic haemostasis, rebleeding, transfusion of > or = 6 units of blood, surgical treatment or any subsequent complication. Use of nonsteroidal anti-inflammatory drugs (27%) was associated with a decreased mortality risk (odds ratio 0.2; P = 0.03). A multivariate analysis showed that the features at presentation which were independently associated with an increased risk of mortality were: a history of cirrhosis, sepsis, shock prior to onset of bleeding, hypo-albuminaemia and elevated serum aminotransferases. CONCLUSION: The prognosis of secondary upper gastrointestinal haemorrhage depends on the underlying diseases and on the general condition of the patient, rather than on the actual cause of bleeding.

Upper gastrointestinal hemorrhage. Comparison of the causes and prognosis in primary and secondary bleeders.

BACKGROUND: Hemorrhage from the upper gastrointestinal (UGI) tract is defined as primary when it is the cause of admission to hospital and as secondary when it complicates the course of patients admitted to hospital for other causes. The objective of this study was to compare the background features, course, and outcome of patients with primary and secondary bleeding. METHODS: All patients who underwent upper endoscopy because of acute UGI bleeding during 1988-91 in a tertiary care university hospital were studied longitudinally. The background features of primary bleeders (n = 321) were compared with those of secondary bleeders (n = 125). From the primary bleeders, a group was matched to the secondary bleeders by age, sex, use of nonsteroidal anti-inflammatory drugs (NSAIDs), and liver disease. The laboratory and endoscopic findings, hospital course, and mortality were compared in the two groups. RESULTS: Secondary bleeders were on the average 5 years older than primary bleeders and were significantly more likely to have ischemic heart disease, chronic lung disease, and chronic renal failure. Use of corticosteroids, H2 blockers, antacids, and anticoagulants in this group was significantly more prevalent, whereas the use of NSAIDs was similar in the two groups. The case-control analysis showed a similar distribution of the causes of bleeding in the two groups. However, rebleeding, endoscopic hemostasis, and complications were more frequent in secondary bleeders. The mortality in secondary bleeders was 28%, compared with 10% in matched primary bleeders, for a relative risk of 3.8 (p = 0.0002). CONCLUSION: Secondary hemorrhage is associated with an increased mortality, which is related to the underlying diseases and not to a difference in the causes of bleeding.