Pervez Sultan

Neuraxial Morphine and Respiratory Depression Finding the Right Balance

Morphine is a drug commonly administered via the epidural or intrathecal route, and is regarded by many as the ‘gold-standard’ single-dose neuraxial opioid due to its postoperative analgesic efficacy and prolonged duration of action. However, respiratory depression is a recognized side effect of neuraxial morphine administered in the perioperative setting. We conducted an extensive review of articles published since 1945 that examine respiratory depression or failure associated with perioperative intrathecal or epidural morphine use.Respiratory depression was previously thought to result from the interaction of opioid in the cerebrospinal fluid with ventral medullary opioid receptors. More recently, the preBötzinger complex located in the medulla has been identified as the site responsible for the decrease in respiratory rate following systemic administration of opioids. Neurons in the preBötzinger complex expressing neurokinin-1 receptors are selectively inhibited by opioids, and therefore are the mediators of opioid-induced respiratory depression.Epidural, intrathecal and plasma pharmacokinetics of opioids are complex, vary between neuraxial compartments, and can even differ within the epidural space itself depending upon level of insertion. Caution should be exercised when prescribing systemic opioids (intravenous or oral) in addition to neuraxial morphine as this can compound the potential for early or delayed respiratory depression.There is a wide range of incidences for respiratory depression following neuraxial morphine in a perioperative setting. Disparity of definitions used for the diagnosis of respiratory depression in the literature precludes identification of the exact incidence of this rare event.The optimal neuraxial opioid dose is a balance between the conflicting demands of providing optimal analgesia while minimizing dose-related adverse effects. Dose-response studies show that neuraxial morphine appears to have an analgesic efficacy ‘ceiling’. The optimal ‘single-shot’ intrathecal dose appears to be 0.075–0.15mg and the ideal ‘single-shot’ epidural morphine dose is 2.5–3.75mg. Analgesic efficacy studies have not been adequately powered to show differences in the incidence of clinically significant respiratory depression. Opioid antagonists such as naloxone to prevent or treat opioid-induced respiratory depression have a number of limitations. Researchers have recently focused on non-opioid drugs such as serotonin receptor agonists. Early evidence suggests that ampakine (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid [AMPA]) receptor modulators may be effective at reducing opioid-induced respiratory depression while maintaining analgesia. Sodium/proton exchanger type 3 (NHE3) inhibitors, which act centrally on respiratory pathways, also warrant further study.

Neuraxial blockade for external cephalic version: a systematic review

BACKGROUND The desire to decrease the number of cesarean deliveries has renewed interest in external cephalic version. The rationale for using neuraxial blockade to facilitate external cephalic version is to provide abdominal muscular relaxation and reduce patient discomfort during the procedure, so permitting successful repositioning of the fetus to a cephalic presentation. This review systematically examined the current evidence to determine the safety and efficacy of neuraxial anesthesia or analgesia when used for external cephalic version. METHODS A systematic literature review of studies that examined success rates of external cephalic version with neuraxial anesthesia was performed. Published articles written in English between 1945 and 2010 were identified using the Medline, Cochrane, EMBASE and Web of Sciences databases. RESULTS Six, randomized controlled studies were identified. Neuraxial blockade significantly improved the success rate in four of these six studies. A further six non-randomized studies were identified, of which four studies with control groups found that neuraxial blockade increased the success rate of external cephalic version. Despite over 850 patients being included in the 12 studies reviewed, placental abruption was reported in only one patient with a neuraxial block, compared with two in the control groups. The incidence of non-reassuring fetal heart rate requiring cesarean delivery in the anesthesia groups was 0.44% (95% CI 0.15-1.32). CONCLUSIONS Neuraxial blockade improved the likelihood of success during external cephalic version, although the dosing regimen that provides optimal conditions for successful version is unclear. Anesthetic rather than analgesic doses of local anesthetics may improve success. The findings suggest that neuraxial blockade does not compromise maternal or fetal safety during external cephalic version.

Endotracheal tube cuff pressure monitoring: a review of the evidence.

Tracheal intubation constitutes a routine part of anaesthetic practice both in the operating theatre as well as in the care of critically ill patients. The procedure is estimated to be performed 13–20 million times annually in the United States alone. There has been a recent renewal of interest in the morbidity associated with endotracheal tube cuff overinflation, particularly regarding the rationale and requirement for endotracheal tube cuff monitoring intra-operatively.

The Effect of Intrathecal Morphine Dose on Outcomes After Elective Cesarean Delivery: A Meta-Analysis.

BACKGROUND:The intrathecal morphine dose achieving optimal analgesia for cesarean delivery while minimizing side effects has not yet been deduced. In this meta-analysis, our objective was to determine whether low- or high-dose intrathecal morphine provides acceptable duration and intensity of analgesia with fewer side effects. METHODS:A literature search (PubMed, EMBASE, MEDLINE, Scopus, Web of Science, and CINAHL) was performed to identify randomized controlled trials involving patients undergoing elective cesarean delivery under spinal anesthesia comparing low-dose (LD; 50–100 &mgr;g) morphine with higher dose (HD; >100–250 &mgr;g). The primary outcome was the time for first request for supplemental analgesia. The secondary outcomes included pain scores, morphine use, maternal side effects (vomiting and pruritus), and Apgar scores. Mean differences (MDs) and odds ratios (ORs) were calculated using random effects modeling with 95% confidence intervals (CIs). RESULTS:Eleven articles met our inclusion criteria. Four hundred eighty patients were recruited in all study groups (233 patients in the HD and 247 in the LD groups). The mean time to first analgesic request was longer (MD, 4.49 hours [95% CI, 1.85–7.13]; P = 0.0008) in the HD group compared with the LD group. Pain scores (0–100 scale) at 12 hours (MD, 2.54 [95% CI, −2.55 to 7.63]; P = 0.33) as well as morphine consumption at 24 hours (MD, 1.31 mg [95% CI, −3.06 to 7.31]; P = 0.42) were not significantly different. The incidence of nausea or vomiting (OR, 0.44 [95% CI, 0.27–0.73]; P = 0.002) and pruritus (OR, 0.34 [95% CI, 0.20–0.59]; P = 0.0001) was lower in the LD group. The incidence of Apgar scores <7 at 1 minute was not different between groups (OR, 1.11 [95% CI, 0.06–20.49]; P = 0.94). CONCLUSIONS:This meta-analysis shows that HDs of intrathecal morphine prolong analgesia after cesarean delivery compared with lower doses. The MD of 4.5 hours (95% CI, 1.9–7.1 and 99% CI, 1.0–8.2 hours) of pain relief must be balanced against the increased risk of maternal pruritus and vomiting. Results from this study can be used by clinicians to weigh the benefits and potential side effects of using HDs of intrathecal morphine for cesarean delivery.

The Effect of patient warming during Caesarean delivery on maternal and neonatal outcomes: a meta-analysis

BACKGROUND Perioperative warming is recommended for surgery under anaesthesia, however its role during Caesarean delivery remains unclear. This meta-analysis aimed to determine the efficacy of active warming on outcomes after elective Caesarean delivery. METHODS We searched databases for randomized controlled trials utilizing forced air warming or warmed fluid within 30 min of neuraxial anaesthesia placement. Primary outcome was maximum temperature change. Secondary outcomes included maternal (end of surgery temperature, shivering, thermal comfort, hypothermia) and neonatal (temperature, umbilical cord pH and Apgar scores) outcomes. Standardized mean difference/mean difference/risk ratio (SMD/MD/RR) and 95% confidence interval (CI) were calculated using random effects modelling (CMA, version 2, 2005). RESULTS 13 studies met our criteria and 789 patients (416 warmed and 373 controls) were analysed for the primary outcome. Warming reduced temperature change (SMD -1.27°C [-1.86, -0.69]; P=0.00002); resulted in higher end of surgery temperatures (MD 0.43 °C [0.27, 0.59]; P<0.00001); was associated with less shivering (RR 0.58 [0.43, 0.79]; P=0.0004); improved thermal comfort (SMD 0.90 [0.36, 1.45]; P=0.001), and decreased hypothermia (RR 0.66 [0.50, 0.87]; P=0.003). Umbilical artery pH was higher in the warmed group (MD 0.02 [0, 0.05]; P=0.04). Eggers test (P=0.001) and contour-enhanced funnel plot suggest a risk of publication bias for the primary outcome of temperature change. CONCLUSIONS Active warming for elective Caesarean delivery decreases perioperative temperature reduction and the incidence of hypothermia and shivering. These findings suggest that forced air warming or warmed fluid should be used for elective Caesarean delivery.

Performance on a probabilistic inference task in healthy subjects receiving ketamine compared with patients with schizophrenia

Evidence suggests that some aspects of schizophrenia can be induced in healthy volunteers through acute administration of the non-competitive NMDA-receptor antagonist, ketamine. In probabilistic inference tasks, patients with schizophrenia have been shown to ‘jump to conclusions’ (JTC) when asked to make a decision. We aimed to test whether healthy participants receiving ketamine would adopt a JTC response pattern resembling that of patients. The paradigmatic task used to investigate JTC has been the ‘urn’ task, where participants are shown a sequence of beads drawn from one of two ‘urns’, each containing coloured beads in different proportions. Participants make a decision when they think they know the urn from which beads are being drawn. We compared performance on the urn task between controls receiving acute ketamine or placebo with that of patients with schizophrenia and another group of controls matched to the patient group. Patients were shown to exhibit a JTC response pattern relative to their matched controls, whereas JTC was not evident in controls receiving ketamine relative to placebo. Ketamine does not appear to promote JTC in healthy controls, suggesting that ketamine does not affect probabilistic inferences.

Pharmacokinetics of Prophylactic Cefazolin in Parturients undergoing Cesarean Delivery

ABSTRACT The objectives of this work were (i) to characterize the pharmacokinetics of cefazolin in pregnant women undergoing elective cesarean delivery and in their neonates; (ii) to assess cefazolin transplacental transmission; (iii) to evaluate the dosing and timing of preoperative, prophylactic administration of cefazolin to pregnant women; and (iv) to investigate the impact of maternal dosing on therapeutic duration and exposure in newborns. Twenty women received 1 g of cefazolin preoperatively. Plasma concentrations of total cefazolin were analyzed from maternal blood samples taken before, during, and after delivery; umbilical cord blood samples obtained at delivery; and neonatal blood samples collected 24 h after birth. The distribution volume of cefazolin was 9.44 liters/h. The values for pre- and postdelivery clearance were 7.18 and 4.12 liters/h, respectively. Computer simulations revealed that the probability of maintaining free cefazolin concentrations in plasma above 8 mg/liter during scheduled caesarean surgery was <50% in the cord blood when cefazolin was administered in doses of <2 g or when it was administered <1 h before delivery. Therapeutic concentrations of cefazolin persisted in neonates >5 h after birth. Cefazolin clearance increases during pregnancy, and larger doses are recommended for surgical prophylaxis in pregnant women to obtain the same antibacterial effect as in nonpregnant patients. Cefazolin has a longer half-life in neonates than in adults. Maternal administration of up to 2 g of cefazolin is effective and produces exposure within clinically approved limits in neonates.

A Cost Analysis of Neuraxial Anesthesia to Facilitate External Cephalic Version for Breech Fetal Presentation

BACKGROUND:In this study, we sought to determine whether neuraxial anesthesia to facilitate external cephalic version (ECV) increased delivery costs for breech fetal presentation. METHODS:Using a computer cost model, which considers possible outcomes and probability uncertainties at the same time, we estimated total expected delivery costs for breech presentation managed by a trial of ECV with and without neuraxial anesthesia. RESULTS:From published studies, the average probability of successful ECV with neuraxial anesthesia was 60% (with individual studies ranging from 44% to 87%) compared with 38% (with individual studies ranging from 31% to 58%) without neuraxial anesthesia. The mean expected total delivery costs, including the cost of attempting/performing ECV with anesthesia, equaled

Amniotic fluid embolism: update and review.

8931 (2.5th–97.5th percentile prediction interval

Inflammation and Epidural-Related Maternal Fever: Proposed Mechanisms.

8541–