Drugs for preventing postoperative nausea and vomiting in adults after general anaesthesia: an abridged Cochrane network meta-analysis.

Postoperative nausea and vomiting is a common adverse effect of anaesthesia. Although dozens of different anti-emetics are available for clinical practice, there is currently no comparative ranking of efficacy and safety of these drugs to inform clinical practice. We performed a systematic review with network meta-analyses to compare, and rank in terms of efficacy and safety, single anti-emetic drugs and their combinations, including 5-hydroxytryptamine3 , dopamine-2 and neurokinin-1 receptor antagonists; corticosteroids; antihistamines; and anticholinergics used to prevent postoperative nausea and vomiting in adults after general anaesthesia. We systematically searched for placebo-controlled and head-to-head randomised controlled trials up to November 2017 (updated in April 2020). We assessed how trustworthy the evidence was using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and Confidence In Network Meta-Analysis (CINeMA) approaches for vomiting within 24 h postoperatively, serious adverse events, any adverse event and drug class-specific side-effects. We included 585 trials (97,516 participants, 83% women) testing 44 single drugs and 51 drug combinations. The studies' overall risk of bias was assessed as low in only 27% of the studies. In 282 trials, 29 out of 36 drug combinations and 10 out of 28 single drugs lowered the risk of vomiting at least 20% compared with placebo. In the ranking of treatments, combinations of drugs were generally more effective than single drugs. Single neurokinin-1 receptor antagonists were as effective as other drug combinations. Out of the 10 effective single drugs, certainty of evidence was high for aprepitant, with risk ratio (95%CI) 0.26 (0.18-0.38); ramosetron, 0.44 (0.32-0.59); granisetron, 0.45 (0.38-0.54); dexamethasone, 0.51 (0.44-0.57); and ondansetron, 0.55 (0.51-0.60). It was moderate for fosaprepitant, 0.06 (0.02-0.21) and droperidol, 0.61 (0.54-0.69). Granisetron and amisulpride are likely to have little or no increase in any adverse event compared with placebo, while dimenhydrinate and scopolamine may increase the number of patients with any adverse event compared with placebo. So far, there is no convincing evidence that other single drugs effect the incidence of serious, or any, adverse events when compared with placebo. Among drug class specific side-effects, evidence for single drugs is mostly not convincing. There is convincing evidence regarding the prophylactic effect of at least seven single drugs for postoperative vomiting such that future studies investigating these drugs will probably not change the estimated beneficial effect. However, there is still considerable lack of evidence regarding safety aspects that does warrant investigation.

Bedside tests for predicting difficult airways: an abridged Cochrane diagnostic test accuracy systematic review.

Although bedside screening tests are routinely used to identify people at high risk of having a difficult airway, their clinical utility is unclear. We estimated the diagnostic accuracy of commonly used bedside examination tests for assessing the airway in adult patients without apparent anatomical abnormalities scheduled to undergo general anaesthesia. We searched for studies that reported our pre-specified bedside index screening tests against a reference standard, published in any language, from date of inception to 16 December 2016, in seven bibliographic databases. We included 133 studies (127 cohort type and 6 case-control) involving 844,206 participants. Overall, their methodological quality (according to QUADAS-2, a standard tool for assessing quality of diagnostic accuracy studies) was moderate to high. Our pre-specified tests were: the Mallampati test (6 studies); modified Mallampati test (105 studies); Wilson risk score (6 studies); thyromental distance (52 studies); sternomental distance (18 studies); mouth opening test (34 studies); and the upper lip bite test (30 studies). Difficult facemask ventilation, difficult laryngoscopy, difficult intubation and failed intubation were the reference standards in seven, 92, 50 and two studies, respectively. Across all reference standards, we found all index tests had relatively low sensitivities, with high variability, but specificities were consistently and markedly higher than sensitivities. For difficult laryngoscopy, the sensitivity and specificity (95%CI) of the upper lip bite test were 0.67 (0.45-0.83) and 0.92 (0.86-0.95), respectively; upper lip bite test sensitivity (95%CI) was significantly higher than that for the mouth opening test (0.22, 0.13-0.33; p < 0.001). For difficult tracheal intubation, the modified Mallampati test had a significantly higher sensitivity (95%CI) at 0.51 (0.40-0.61) compared with mouth opening (0.27, 0.16-0.41; p < 0.001) and thyromental distance (0.24, 0.12-0.43; p < 0.001). Although the upper lip bite test showed the most favourable diagnostic test accuracy properties, none of the common bedside screening tests is well suited for detecting unanticipated difficult airways, as many of them are missed.

Patient-controlled analgesia with remifentanil vs. alternative parenteral methods for pain management in labour: a Cochrane systematic review.

We aimed to assess the effectiveness of remifentanil used as intravenous patient-controlled analgesia for the pain of labour. We performed a systematic literature search in December 2015 (updated in December 2016). We included randomised, controlled and cluster-randomised trials of women in labour with planned vaginal delivery receiving patient-controlled remifentanil compared principally with other parenteral and patient-controlled opioids, epidural analgesia and continuous remifentanil infusion or placebo. The primary outcomes were patient satisfaction with pain relief and the occurrence of adverse events for mothers and newborns. We assessed risk of bias for each included study and applied the GRADE approach for the quality of evidence. We included total zero event trials, using a constant continuity correction of 0.01 and a random-effect meta-analysis. Twenty studies were included in the qualitative analysis; within these, 3713 participants were randomised and 3569 analysed. Most of our pre-specified outcomes were not studied in the included trials. However, we found evidence that women using patient-controlled remifentanil were more satisfied with pain relief than women receiving parenteral opioids (four trials, 216 patients, very low quality evidence) with a standardised mean difference ([SMD] 95%CI) of 2.11 (0.72-3.49), but were less satisfied than women receiving epidural analgesia (seven trials, 2135 patients, very low quality evidence), -0.22 (-0.40 to -0.04). Data on adverse events were sparse. However, the relative risk (95%CI) for maternal respiratory depression for patient-controlled remifentanil compared with epidural analgesia (three trials, 687 patients, low-quality evidence) was 0.91 (0.51-1.62). Compared with continuous intravenous infusion of remifentanil (two trials, 135 patients, low-quality evidence) no conclusion could be reached as all study arms showed zero events. The relative risk (95%CI) of Apgar scores less than 7 at 5 min after birth compared with epidural analgesia (five trials, 1322 participants, low-quality evidence) was 1.26 (0.62-2.57).

Efficacy and safety of intravenous lidocaine for postoperative analgesia and recovery after surgery: a systematic review with trial sequential analysis.

BACKGROUND: Improvement of postoperative pain and other perioperative outcomes remain a significant challenge and a matter of debate among perioperative clinicians. This systematic review aims to evaluate the effects of perioperative i.v. lidocaine infusion on postoperative pain and recovery in patients undergoing various surgical procedures. METHODS: CENTRAL, MEDLINE, EMBASE, and CINAHL databases and ClinicalTrials.gov, and congress proceedings were searched for randomized controlled trials until May 2014, that compared patients who did or did not receive continuous perioperative i.v. lidocaine infusion. RESULTS: Forty-five trials (2802 participants) were included. Meta-analysis suggested that lidocaine reduced postoperative pain (visual analogue scale, 0 to 10 cm) at 1-4 h (MD -0.84, 95% CI -1.10 to -0.59) and at 24 h (MD -0.34, 95% CI -0.57 to -0.11) after surgery, but not at 48 h (MD -0.22, 95% CI -0.47 to 0.03). Subgroup analysis and trial sequential analysis suggested pain reduction for patients undergoing laparoscopic abdominal surgery or open abdominal surgery, but not for patients undergoing other surgeries. There was limited evidence of positive effects of lidocaine on postoperative gastrointestinal recovery, opioid requirements, postoperative nausea and vomiting, and length of hospital stay. There were limited data available on the effect of systemic lidocaine on adverse effects or surgical complications. Quality of evidence was limited as a result of inconsistency (heterogeneity) and indirectness (small studies). CONCLUSIONS: There is limited evidence suggesting that i.v. lidocaine may be a useful adjuvant during general anaesthesia because of its beneficial impact on several outcomes after surgery.

Effect of body mass index on the ED50 volume of bupivacaine 0.5% for supraclavicular brachial plexus block.

BACKGROUND: The aim of this study was to determine whether the ED(50) dose of bupivacaine 0.5% for supraclavicular brachial plexus block increases with increasing body mass index (BMI). METHODS: This double-blind, non-randomized trial followed an up-and-down sequential allocation design. Adult patients undergoing elective upper limb surgery under ultrasound-guided supraclavicular brachial block were recruited. A preliminary study was used to guide the dosing schedule for the main study in which patients were divided into three groups according to their BMI (Group A, BMI >27 kg m(-2); Group B, BMI 24-27 kg m(-2); Group C, BMI <24 kg m(-2)). The study design and analysis followed Dixon's small sample model using a 'nominal' sample size of six per group. RESULTS: Twenty-one patients were recruited to the preliminary study. Using isotonic regression, the ED(50) for bupivacaine 0.5% was estimated to be 8.9 ml [95% confidence interval (CI) 7.8-15.9]. In comparison, the ED(50) volume was found to be 10.8 ml (95% CI 5.9-19.7) using the Dixon-Massey formula. In the main study, six patients were recruited in each group with mean (range) BMI of 31.5 (27.2-38.8) kg m(-2) in Group A, 25.6 (24.4-26.3) kg m(-2) in Group B, and 21.6 (19.7-23.8) kg m(-2) in Group C. The ED(50) (95% CI) for Groups A, B, and C were 8.9 (6.2-12.7), 10.7 (7.5-15.4), and 13.4 (9.3-19.1) ml, respectively (P=0.05 for Group A vs Group C). CONCLUSIONS: Our study demonstrates that the ED(50) of bupivacaine 0.5% does not increase with an increase in BMI. We found evidence of a possible inverse relationship between ED(50) and BMI.

Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics.

BACKGROUND: Spinal anaesthesia has been in use since the turn of the late nineteenth century. During the last decade there has been an increase in the number of reports implicating lidocaine as a possible cause of temporary and permanent neurologic complications after spinal anaesthesia. Follow-up of patients who received uncomplicated spinal anaesthesia revealed that some of them developed pain in the lower extremities after an initial full recovery. This painful condition that occurs in the immediate postoperative period was named "transient neurologic symptoms" (TNS). OBJECTIVES: To study the frequency of TNS and neurologic complications after spinal anaesthesia with lidocaine, compared to other local anaesthetics. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (CENTRAL), (The Cochrane Library, Issue 1, 2005); MEDLINE (1966 to January 2005); EMBASE (1980 to week 6, 2005); LILACS (March 2005); and handsearched the reference lists of trials and review articles. SELECTION CRITERIA: We included all randomized and pseudo-randomized studies comparing the frequency of TNS and of neurologic complications after spinal anaesthesia with lidocaine as compared to other local anaesthetics. DATA COLLECTION AND ANALYSIS: Two authors independently evaluated the quality of the relevant studies and extracted the data from the included studies. MAIN RESULTS: Fifteen trials, reporting 1437 patients, 120 of whom developed transient neurologic symptoms, were included in the analysis. The use of lidocaine for spinal anaesthesia increased the risk of developing TNS. There was no evidence that this painful condition was associated with any neurologic pathology; the symptoms disappeared spontaneously by the fifth postoperative day. The relative risk (RR) for developing TNS after spinal anaesthesia with lidocaine as compared to other local anaesthetics (bupivacaine, prilocaine, procaine, levobupivacaine and ropivacaine) was 7.16 (95% confidence interval (CI) 4.02, 12.75). AUTHORS' CONCLUSIONS: The risk of developing TNS after spinal anaesthesia with lidocaine was significantly higher than when bupivacaine, prilocaine and procaine were used. The term "TNS", which implies a positive neurologic finding, should not be used for this painful condition. One study about the impact of TNS on patient satisfaction and functional impairment demonstrated that non-TNS patients were more satisfied and had less functional impairment after surgery than TNS patients, but this did not influence their willingness to recommend spinal anaesthesia.

Transient neurologic symptoms (TNS) following spinal anaesthesia with lidocaine versus other local anaesthetics.

BACKGROUND: Spinal anaesthesia has been in use since the turn of the late 19th century. The most serious complication of this technique is damage to the spinal cord or nerve roots resulting in lasting neurologic sequelae. Such serious adverse effects seldom happen. There has been an increase in the number of reports during the last nine years implicating lidocaine as a possible cause of temporary and permanent neurologic complications after spinal anaesthesia. Follow-up of patients who received uncomplicated spinal anaesthesia revealed that some of them developed pain in the lower extremities after an initial full recovery. This painful condition that occurs in the immediate post-operative period was named "transient neurologic symptoms" (TNS). OBJECTIVES: The objectives of this review were to study the frequency of TNS and neurologic complications after spinal anaesthesia with lidocaine, compared to other local anaesthetics. SEARCH STRATEGY: Trials were identified by computerized searches of the Cochrane Controlled Trials Register (4th Quarter 2002), MEDLINE (1966 - January 2003), LILAC database, EMBASE (1980 - week 51, 2002), and by checking the reference lists of trials and review articles. SELECTION CRITERIA: All randomized and pseudo-randomized studies comparing the frequency of TNS and of neurologic complications after spinal anaesthesia with lidocaine as compared to other local anaesthetics. DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated the quality of the relevant studies and extracted the data from the included studies. MAIN RESULTS: Fourteen trials, reporting 1,349 patients, 117 of whom developed transient neurologic symptoms, were included in the analysis. The use of lidocaine for spinal anaesthesia increased the risk of developing TNS. There was no evidence that this painful condition was associated with any neurologic pathology as it was clearly documented that no positive neurologic findings were present in any patient with TNS; the symptoms disappeared spontaneously by the fifth postoperative day. The relative risk for developing TNS after spinal anaesthesia with lidocaine as compared to other local anaesthetics (bupivacaine, prilocaine, procaine and mepivacaine) was 4.35 (95% Confidence Interval: 1.98, 9.54). REVIEWER'S CONCLUSIONS: The risk of developing TNS after spinal anaesthesia with lidocaine was significantly higher than when bupivacaine, prilocaine and procaine were used. The term "TNS", which implies a positive neurologic finding, should not be used for this painful condition, which is in fact comparable to another common adverse effect after spinal anaesthesia - lower back pain. How much the pain in the lower extremities influences patient satisfaction is not elucidated clearly in the literature.

Effects of intrathecal morphine on the ventilatory response to hypoxia.

BACKGROUND: Intrathecal administration of morphine produces intense analgesia, but it depresses respiration, an effect that can be life-threatening. Whether intrathecal morphine affects the ventilatory response to hypoxia, however, is not known. METHODS: We randomly assigned 30 men to receive one of three study treatments in a double-blind fashion: intravenous morphine (0.14 mg per kilogram of body weight) with intrathecal placebo; intrathecal morphine (0.3 mg) with intravenous placebo; or intravenous and intrathecal placebo. The selected doses of intravenous and intrathecal morphine produce similar degrees of analgesia. The ventilatory response to hypercapnia, the subsequent response to acute hypoxia during hypercapnic breathing (targeted end-tidal partial pressures of expired oxygen and carbon dioxide, 45 mm Hg), and the plasma levels of morphine and morphine metabolites were measured at base line (before drug administration) and 1, 2, 4, 6, 8, 10, and 12 hours after drug administration. RESULTS: At base line, the mean (+/-SD) values for the ventilatory response to hypoxia (calculated as the difference between the minute ventilation during the second full minute of hypoxia and the fifth minute of hypercapnic ventilation) were similar in the three groups: 38.3+/-23.2 liters per minute in the placebo group, 33.5+/-16.4 liters per minute in the intravenous-morphine group, and 30.2+/-11.6 liters per minute in the intrathecal-morphine group (P=0.61). The overall ventilatory response to hypoxia (the area under the curve) was significantly lower after either intravenous morphine (20.2+/-10.8 liters per minute) or intrathecal morphine (14.5+/-6.4 liters per minute) than after placebo (36.8+/-19.2 liters per minute) (P=O.003). Twelve hours after treatment, the ventilatory response to hypoxia in the intrathecal-morphine group (19.9+/-8.9 liters per minute), but not in the intravenous-morphine group (30+/-15.8 liters per minute), remained significantly depressed as compared with the response in the placebo group (40.9+/-19.0 liters per minute) (P= 0.02 for intrathecal morphine vs. placebo). Plasma concentrations of morphine and morphine metabolites either were not detectable after intrathecal morphine or were much lower after intrathecal morphine than after intravenous morphine. CONCLUSIONS: Depression of the ventilatory response to hypoxia after the administration of intrathecal morphine is similar in magnitude to, but longer-lasting than, that after the administration of an equianalgesic dose of intravenous morphine.

Dysphotopsia in phakic and pseudophakic patients: incidence and relation to intraocular lens type(2).

PURPOSE: To determine the relationship between various intraocular lens (IOL) types and the incidence of unwanted light images. SETTING: The Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. METHODS: A telephone questionnaire was administered to 302 postoperative patients who had received 1 of 6 commonly used IOLs between January and September 1998. Patients were included only if they had uneventful cataract surgery, no additional ocular pathology, and a postoperative best corrected visual acuity of 20/25 or better. A control group of 50 patients with the diagnosis of presbyopia only also participated in the questionnaire. Patients reported on incidence of glare, light sensitivity, and unwanted images. The data were analyzed for statistically significant relationships between incidence of photopsias and IOL type. RESULTS: The AcrySof 5.5 mm, AcrySof 6.0 mm, and SI-40 groups reported significantly more unwanted images than the control group (P =.0014). The 2 AcrySof groups also reported a greater incidence of light to the side causing a central flash, and the SI-40 group, a higher incidence of glare. The control group was more likely to experience symptoms of glare than any pseudophakic group. Overall, a mean of 49% of patients reported some light-related phenomenon postoperatively. The majority in all groups reported being satisfied with their eyesight despite the light-related problems. CONCLUSIONS: A significant number of pseudophakic patients reported symptoms of dysphotopsia. Patients who received an acrylic IOL with flattened edges were at increased risk of experiencing images associated with edge reflections. The SI-40 lens group, although less than the AcrySof groups, reported a higher incidence of glare than the non-AcrySof groups; however, it also had the highest number of patients still driving at night. The phakic population commonly experienced glare reported as more severe than several of the IOL groups.

Intrathecal fentanyl is superior to intravenous ondansetron for the prevention of perioperative nausea during cesarean delivery with spinal anesthesia.

This study compares intrathecal (IT) fentanyl with IV ondansetron for preventing intraoperative nausea and vomiting during cesarean deliveries performed with spinal anesthesia. Thirty healthy parturients presenting for elective cesarean delivery with standardized bupivacaine spinal anesthesia were randomized to receive 20 microg IT fentanyl (Group F) or 4 mg IV ondansetron (Group O) by using double-blinded methodology. At eight specific intervals during the surgery, a blinded observer questioned the patient about nausea (1 = nausea, 0 = no nausea), observed for the presence of retching or vomiting (1 = vomiting or retching, 0 = no vomiting or retching), and recorded a verbal pain score (0-10, 0 = no pain, 10 = worst pain imaginable). Cumulative nausea, vomiting, and pain scores were calculated as the sum of the eight measurements. Intraoperative nausea was decreased in the IT fentanyl group compared with the IV ondansetron group: the median (interquartile range) difference in nausea scores was 1 (1, 2), P = 0.03. The incidence of vomiting and treatment for vomiting was not different (P = 0.7). The IT fentanyl group had a lower cumulative perioperative pain score than the IV ondansetron group; the median difference in the cumulative pain score was 12 (8, 16) (P = 0.0007). The IT fentanyl group required less supplementary intraoperative analgesia. The median difference in the cumulative fentanyl dose was 100 (75, 100) microg fentanyl, (P = 0.0002).

Multiple dose pharmacokinetics of oral transmucosal fentanyl citrate in healthy volunteers.

BACKGROUND: Oral transmucosal fentanyl citrate (OTFC) is a solid form of fentanyl that delivers the drug through the oral mucosa. The clinical utility of multiple doses of OTFC in the treatment of "breakthrough" cancer pain is under evaluation. The aim of this study was to test the hypothesis that the pharmacokinetics of OTFC do not change with multiple dosing. METHODS: Twelve healthy adult volunteers received intravenous fentanyl (15 microg/kg) or OTFC (three consecutive doses of 800 microg) on separate study sessions. Arterial blood samples were collected for determination of fentanyl plasma concentration by radioimmunoassay. The descriptive pharmacokinetic parameters (maximum concentration, minimum concentration, and time to maximum concentration) were identified from the raw data and subjected to a nonparametric analysis of variance. Population pharmacokinetic models for all subjects and separate models for each subject were developed to estimate the pharmacokinetic parameters of fentanyl after multiple OTFC doses. RESULTS: The shapes of the profiles of plasma concentration versus time for each dose of OTFC were grossly similar. No change was noted for maximum concentration or time to maximum concentration over the three doses, while minimum concentration did show a significantly increasing trend. Terminal half-lives for intravenous fentanyl and OTFC were similar. A two-compartment population pharmacokinetic model adequately represented the central tendency of the data from all subjects. Individual subject data were best described by either two- or three-compartment pharmacokinetic models. These models demonstrated rapid and substantial absorption of OTFC that did not change systematically with time and multiple dosing. CONCLUSIONS: The pharmacokinetics of OTFC were similar among subjects and did not change with multiple dosing. Multiple OTFC dosing regimens within the dosage schedule examined in this study can thus be formulated without concern about nonlinear accumulation.

Delays in the detection of hypoxemia due to site of pulse oximetry probe placement.

STUDY OBJECTIVES: To determine if there were any differences in the time to detect hypoxemia related to the site of peripheral pulse oximetry (ear, hand, and foot) during the rapid induction of hypoxemia in healthy volunteers. DESIGN: Repeated-measures, longitudinal, observational study. SETTING: Anesthesia clinical research area of the Department of Anesthesiology. PATIENTS: 13 healthy volunteers, aged 18 to 44 years. INTERVENTIONS: Nellcor N-200 (Nellcor, Inc., Pleasanton, CA) oximeter probes were placed at the ear, hand, and foot. All units were turned on simultaneously with averaging times set for 5 seconds and signals sampled at 2 Hz. A computer-controlled anesthesia circuit was employed to induce mild hypercapnia and hyperoxia (end-tidal gas partial pressures: PETCO2 = 42 +/- 2 mmHg and PETO2 = 130 mmHg) for 5 minutes. PETO2 was then decreased to 45 +/- 2 mmHg over 60 seconds and held at that value for 5 minutes. MEASUREMENTS AND MAIN RESULTS: The mean differences in time (sec) for pulse oximeters to detect hypoxemia (read less than 90%) between probe sites were determined and compared. The following mean differences in time (sec) for pulse oximeters to detect hypoxemia (read less than 90%) between probe sites were found: ear-hand = 6; hand-foot = 57; ear-foot = 63. Paired t-tests revealed statistically significant mean time delay differences of 51 seconds (p < 0.005) and 57 seconds (p < 0.005) for ear-hand versus hand-foot and for ear-hand versus ear-foot, respectively. CONCLUSIONS: In healthy volunteers, significant delays in the detection of acute hypoxemia by pulse oximetry occur when pulse oximeters are placed at the toe as compared with probes at either the ear or hand.

Rapid onset of ulnar nerve dysfunction during transient occlusion of the brachial artery.

UNLABELLED: Perioperative ulnar neuropathy is a complication that occurs even in patients who seem to be appropriately padded and positioned. The disproportionately high incidence of postoperative ulnar nerve injury compared with the median and radial nerves has largely been attributed to its vulnerability to compression or stretch at the cubital tunnel. Some clinical and laboratory evidence suggests that compromise of perfusion to the upper extremity may also play a role in this complication. To determine whether the ulnar nerve is more sensitive to ischemia of the upper extremity, we studied 10 men during general anesthesia. Somatosensory evoked potentials of the radial, median, and ulnar nerves were simultaneously recorded during general anesthesia with the brachial artery occluded proximal to the cubital fossa. All three nerves showed rapid changes in signal amplitude in response to occlusion of the brachial artery, but the amplitude of the ulnar nerve was affected earlier and to a greater degree. Compared with the median nerve, the change in ulnar nerve signal amplitude during ischemia was significantly greater after 4 min (P = 0.002). This trend persisted at 6 and 8 min (P = 0.008). At 4, 6, and 8 min of ischemia, the ulnar nerve likewise showed a greater decrease in amplitude compared with the radial nerve, with corresponding P values of 0.015, 0.008, and 0.008. We conclude that the ulnar nerve is more sensitive to ischemia of the upper extremity compared with the radial and median nerves. In addition to its increased vulnerability at the elbow, compromise of arterial flow may contribute to some cases of postoperative ulnar neuropathy. IMPLICATIONS: Postoperative ulnar neuropathy is thought to result from compression or stretch of the ulnar nerve at the elbow. However, patients may sustain this complication despite careful padding and positioning. This study suggests that the ulnar nerve may also be unusually sensitive to decreases in blood supply to the arm. Care should not only to properly position and pad the elbows, but also to ensure adequate perfusion of the upper extremities.

Dose proportionality and pharmacokinetics of oral transmucosal fentanyl citrate.

BACKGROUND: The pharmacokinetics of a single dose (15 microg/kg) of oral transmucosal fentanyl citrate (OTFC) have been characterized. A range of doses may eventually be used in clinical practice. The goal of this study was to determine if the pharmacokinetics of OTFC are dose proportional for doses ranging from 200 to 1,600 microg. METHODS: Twelve healthy male volunteers were studied on four different occasions, receiving 200, 400, 800, and 1,600 microg OTFC in a double-blind, randomized protocol. Venous blood samples were collected at selected times during and after dosing for a 24-h period and assayed for fentanyl using a radioimmunoassay. Maximum concentration, time to maximum concentration, area under the curve, and elimination half-life were determined for each dose administered. In addition, respiratory rate, need for verbal prompting to breathe, and supplemental oxygen requirements were noted. RESULTS: Mean fentanyl concentration time curves were similarly shaped with increasing doses. Both peak concentrations and area under the curve increased linearly with an increase in dose, whereas time to reach peak serum concentrations did not vary significantly between doses. Except for the 200-microg dose, the apparent elimination half-life remained relatively constant (358-386 min). The incidence of low respiratory rate, supplemental oxygen requirement, and number of breathing prompts significantly increased with increasing doses. CONCLUSIONS: Oral transmucosal fentanyl citrate exhibits dose-proportional pharmacokinetics over the dose range of 200-1,600 microg.

The dose-response pharmacology of intrathecal sufentanil in female volunteers.

The pharmacologic effects of intrathecal sufentanil (ITS) beyond what is clinically administered (10 microg) are not known. We observed 18 healthy, young, adult female volunteers who received 12.5, 25, or 50 microg of ITS in a randomized, double-blind fashion for 11 h. Analgesia was assessed by pressure algometry at the tibia. Respiratory function was assessed by pulse oximetry, respiratory rate, arterial blood gas, the ventilatory response to CO2, and a respiratory intervention score (RIS). The incidence and severity of side effects also were documented. Serum sufentanil levels were measured for 4 h after ITS administration. We found that ITS produced statistically significant changes in algometry, doubling the pressure required to produce moderate pain. However, doses of ITS greater than 12.5 microg failed to produce proportionate increases in the duration or intensity of analgesia. All doses of ITS produced significant respiratory depression, but only the RIS was significantly related to ITS dose. Neither respiratory rate nor sedation reliably predicted hypoxemia. Supplemental oxygen by nasal cannula consistently prevented pulse oximeter readings below 90%. Serum sufentanil concentrations were related to ITS dose in a statistically significant manner, reached clinically significant concentrations, and followed a time course similar to analgesia and measures of respiratory depression. However, there was no significant increase in measured analgesia associated with the increases in serum sufentanil concentrations. We conclude that in our volunteer model of lower extremity pain, administering ITS in doses larger than 12.5 microg does not improve the speed of onset, magnitude, or duration of analgesia and only causes dose-related increases in serum sufentanil concentrations, which may augment respiratory depression.

Duration of intrathecal labor analgesia: early versus advanced labor.

Early first-stage labor pain is primarily visceral in origin. Increasing pain intensity and transition to somatic nociceptive input characterizes late first- and second-stage labor pain. The effect of this change in nociceptive input on the duration of intrathecal labor analgesia has not been well studied. This prospective cohort observational study compares the duration of intrathecal labor analgesia after intrathecal injections made in early labor (3- to 5-cm cervical dilation) and those made in more advanced labor (7- to 10-cm cervical dilation). Forty-one parturients (18 in early labor and 23 in advanced labor) received intrathecal sufentanil (10 micrograms) and bupivacaine (2.5 mg) as part of a combined spinal-epidural technique. Patients rated their pain using a 0-10 verbal pain scale prior to intrathecal injection and every 20 min thereafter. Duration of analgesia was defined as the lesser of time until the pain score exceeded 5 or until a request for supplemental epidural analgesia was made. The duration of spinal analgesia was significantly less when intrathecal injection was made in advanced labor (120 +/- 26 min) compared with early labor (163 +/- 57 min, P < 0.01). We conclude that cervical dilation and stage of labor significantly impact the effective duration of intrathecal sufentanil/ bupivacaine labor analgesia.

Transesophageal echocardiography: an objective tool in defining maximum ventricular response to intravenous fluid therapy.

Ventricular preload is an important determinant of cardiac function, which is indirectly measured in the clinical setting by the pulmonary capillary wedge pressure (PCWP). Transesophageal echocardiography (TEE) is rapidly gaining acceptance as a monitor of cardiac function. Although it provides high-resolution images of cardiac structures, clinical assessment of ventricular preload using TEE has been subjective, since quantitative measurements have been difficult to perform in a timely fashion. Automated border detection (ABD) is a new technology used in conjunction with TEE that allows quantitative real-time, two-dimensional measurement of cavity areas. To determine whether enddiastolic area (EDA) measured by ABD can be used to determine an appropriate end point for intravenous fluid administration, nine mongrel dogs were studied. Anesthetized animals were hemorrhaged to achieve a central venous pressure of 0-5 mm Hg. Each animal was then given intravenous fluid (autologous blood followed by hetastarch) until a peak in thermodilution cardiac output (CO) was achieved. Measures of PCWP, EDA, CO, and left ventricular stroke work (LVSW) were obtained after each fluid bolus. Bivariate plots displaying administered volume versus CO, LVSW, and EDA revealed parallel curves for each of these variables with peaks evident at cumulative volumes of 50-55 mL/kg. Multiple regression with mixed model analysis of covariance was performed to determine the significance of EDA in relation to changes in CO and LVSW. Analysis was likewise performed comparing the relationship between PCWP and changes in CO or LVSW. A significant relationship was demonstrated when comparing EDA to changes in CO and LVSW (P = 0.03 and P < 0.0001, respectively). Similar analysis comparing PCWP to changes in CO and LVSW failed to demonstrate a significant relationship (P = 0.54 and P = 0.36, respectively). These data suggest that changes in EDA measured using TEE with ABD are related to trends in cardiac function and can suggest an appropriate end point for intravenous fluid administration as defined by maximum CO and LVSW. PCWP did not demonstrate a significant relationship to changes in CO and LVSW.

The effect of prior dural puncture on cisternal cerebrospinal fluid morphine concentrations in sheep after administration of lumbar epidural morphine.

Combined spinal epidural anesthesia has become increasingly popular as a method of providing rapid onset of analgesia or surgical block with access for further administration of analgesics or anesthetics. No in vivo studies have evaluated the relationship between dural puncture and drug transfer from the epidural space to the cerebrospinal fluid (CSF). To determine whether morphine administered in the epidural space adjacent to a dural puncture results in increased CSF concentrations at the cisterna magna (CM), 12 adult ewes were studied. Each animal was assigned to one of three groups. Animals in Group 1 served as a control and received no dural puncture. Animals in Group 2 received a dural puncture with a 25-gauge (G) Whitacre needle, while Group 3 animals received a dural puncture with an 18-G Tuohy needle. One hour after dural puncture, each animal was given epidural morphine, 0.2 mg/kg. Six hours after the administration of epidural morphine, CSF from the CM was sampled and analyzed by gas chromatography-mass spectrometry for morphine concentration. The mean morphine concentration at the CM for Group 1 (control) was 22 +/- 12 ng/mL, whereas animals with 25-G and 18-G dural punctures had concentrations of 154 +/- 32 ng/mL and 405 +/- 53 ng/mL, respectively (P = 0.0005). These data demonstrate that a significant increase in CSF morphine concentration at the brainstem will occur when lumbar epidural morphine is administered adjacent to a dural puncture. Furthermore, the increase in CSF morphine concentration is positively correlated with the size of the needle producing the dural puncture. These findings highlight the potential for delayed respiratory depression when epidural opiate administration follows a dural puncture.