An open-label randomized controlled clinical trial for comparison of continuous phenylephrine versus norepinephrine infusion in prevention of spinal hypotension during cesarean delivery.

BACKGROUND: During spinal anesthesia for cesarean delivery phenylephrine is the vasopressor of choice but can cause bradycardia. Norepinephrine has both ß- and α-adrenergic activity suitable for maintaining blood pressure with less bradycardia. We hypothesized that norepinephrine would be superior to phenylephrine, requiring fewer rescue bolus interventions to maintain blood pressure. METHODS: Eighty-five parturients having spinal anesthesia for elective cesarean delivery were randomized to Group P (phenylephrine 0.1µg/kg/min) or Group N (norepinephrine 0.05µg/kg/min) fixed-rate infusions. Rescue bolus interventions of phenylephrine 100µg for hypotension, or ephedrine 5mg for bradycardia with hypotension, were given as required to maintain systolic blood pressure. Maternal hemodynamic variables were measured non-invasively. RESULTS: There was no difference between groups in the proportion of patients who required rescue vasopressor boluses (Group P: 65.8% [n=25] vs. Group N: 48.8% [n=21], P=0.12). The proportion of patients who received ⩾1 bolus of phenylephrine was similar between groups (Group P: 52.6% [n=20] vs. Group N: 46.5% [n=20], P=0.58). However, more patients received ⩾1 bolus of ephedrine in the phenylephrine group (Group P: 23.7% [n=9] vs. Group N: 2.3% [n=1], P<0.01). The incidence of emesis was greater in the phenylephrine group (Group P: 26.3% vs. Group P: 16.3%, P<0.001). Hemodynamic parameters including heart rate, the incidence of bradycardia, blood pressure, cardiac output, cardiac index, stroke volume, and systemic vascular resistance and neonatal outcome were similar between groups (all P<0.05). CONCLUSION: Norepinephrine fixed-rate infusion has efficacy for preventing hypotension and can be considered as an alternative to phenylephrine.

Increasing operating room efficiency through electronic medical record analysis.

We used electronic medical record (EMR) analysis to determine errors in operating room (OR) time utilisation. Over a two year period EMR data of 44,503 surgical procedures was analysed for OR duration, on-time, first case, and add-on time performance, within 19 surgical specialties. Maximal OR time utilisation at our institution could have saved over 302,620 min or 5,044 hours of OR efficiency over a two year period. Most specialties (78.95%) had inaccurately scheduled procedure times and therefore used the OR more than their scheduled allotment time. Significant differences occurred between the mean scheduled surgical durations (101.38 ± 87.11 min) and actual durations (108.18 ± 102.27 min; P < 0.001). Significant differences also occurred between the mean scheduled add-on durations (111.4 ± 75.5 min) and the actual add-on scheduled durations (118.6 ± 90.1 minutes; P < 0.001). EMR quality improvement analysis can be used to determine scheduling error and bias, in order to improve efficiency and increase OR time utilisation.

Ultrasound decreases the failed labor epidural rate in resident trainees.

BACKGROUND: Epidural analgesia is widely used for pain relief during labor. The purpose of this study was to determine if ultrasound measurement of the depth from skin to epidural space before the epidural technique decreases the failure rate of labor analgesia. A secondary objective was to correlate ultrasound depth to the epidural space with actual depth of the needle at placement. METHODS: In this prospective, randomized, non-blinded study, 370 parturients requesting labor epidural analgesia were randomized to receive their epidural technique by first year anesthesia residents with or without prior ultrasound determination of epidural space depth. Outcome variables included the incidence of epidural catheter replacement for failed analgesia and the number of epidural attempts and accidental dural punctures. RESULTS: The ultrasound group had fewer epidural catheter replacements (P<0.02), and epidural placement attempts (P<0.01) compared to the control group. Pearson's correlation coefficients comparing the actual versus ultrasound estimated depth to the epidural space in the longitudinal median and transverse planes were 0.914 and 0.909, respectively. Pearson's correlation coefficient comparing the ultrasound estimated depths to the epidural space in the transverse and longitudinal median planes was 0.940. No significant differences were noted with respect to staff interventions, top-ups, accidental dural punctures, and delivery outcome. CONCLUSIONS: Ultrasound measurement of the epidural space depth before epidural technique placement decreases the rate of epidural catheter replacements for failed labor analgesia, and reduces the number of epidural attempts when performed by first year residents and compared to attempts without ultrasound guidance.

The incidence of maternal fever during labor is less with intermittent than with continuous epidural analgesia: a randomized controlled trial.

BACKGROUND: This prospective, randomized study was performed to see if intermittent labor epidural analgesia was protective against maternal intrapartum fever, compared to continuous epidural infusion. METHODS: Ninety-two healthy, term, nulliparous women in spontaneous labor were assigned to either intermittent (ILEA) or continuous labor epidural analgesia (CLEA), 46 in each group. In both groups, epidural analgesia was established with fentanyl 100 microg, and 8 mL of either 0.125% bupivacaine with fentanyl 0.0002%, or 0.1% ropivacaine with fentanyl 0.0002%. Maintenance in the CLEA group was with the same bupivacaine/fentanyl or ropivacaine/fentanyl solutions at 10-15 mL/h. In the ILEA group, additional boluses of the same solution were given as needed. Maternal tympanic temperature was measured before epidural insertion, 4-hourly during labor and 4 h post partum. Fever was defined as a temperature of > or =38 degrees C. Newborn temperature was noted within 60 min of birth. RESULTS: The incidence of fever in ILEA was significantly lower at four hours (2/42, vs. 10/44 in CLEA, P=0.036). No significant differences were detected at other time periods. Mean maternal temperatures did not differ between groups at any time. There were no differences in neonatal temperature or neonatal sepsis evaluation rate (CLEA vs. ILEA 0/46 vs. 2/43, P=0.45). CONCLUSIONS: Intermittent epidural injections appear to protect against intrapartum fever in the first 4 hours of labor analgesia, compared to continuous infusion. This may be due to intermittent partial recovery of heat loss mechanisms between injections. Neonatal sepsis evaluation rates were similar in the two groups.

Comparative efficacy of modified vaccinia Ankara (MVA) as a potential replacement smallpox vaccine.

International concern over the potential consequences of a Bioterrorist or Biowarfare associated release of variola virus have prompted renewed interest in the vaccines for smallpox. The traditional live, replicating vaccine strains are subject to novel safety concerns associated with historical production methods in domesticated ruminants and the additional hazards that vaccinia virus poses for people with immune system abnormalities or a history of eczematous skin conditions. In this study we have examined the longevity and efficacy of immunity induced by a non-replicating smallpox vaccine candidate, modified vaccinia Ankara (MVA) in a murine model using intranasal and aerosol routes of infection. Two-step vaccinations of MVA followed by traditional Lister vaccine are compared with either Lister alone or MVA alone, and the longevity of the protection induced by MVA is assessed. MVA is found to be broadly similar to Lister. Although protection is shown to decay with time, when administered at a standard human dose the longevity of protection induced by MVA is comparable to that induced by Lister.

Chorioamnionitis, not epidural analgesia, is associated with maternal fever during labour.

PURPOSE: Maternal fever is associated with chorioamnionitis and has been linked to labour epidural analgesia (LEA). The purpose of this study was to determine possible associations between LEA and chorioamnionitis, maternal fever, operative delivery rate, and neonatal outcome. METHODS: Data from 14,073 patients were entered into a database over a two-year period. From this database, 62 nulliparous parturients with clinical chorioamnionitis (amnionitis), but without LEA were identified (Group I). Two other groups who received LEA were matched for parity and gestation: Group II - LEA with concomitant amnionitis (n=50) and, Group III - LEA without concomitant amnionitis (n=201). The diagnosis of chorioamnionitis was confirmed by histologic examination. Results are expressed as mean +/- SD and analyzed at P <0.05 using ANOVA or Chi-square. RESULTS: No differences were noted among the groups in the operative delivery rate or Apgar scores at five minutes. The percentage of patients with maternal fever during labour (38.0 degrees C) with amnionitis was significantly less in Group III compared to the other groups (100% in both Groups I and II vs 1.0% in Group III; P=0.000). Likewise, Group III had a lower percentage of neonates with Apgar scores <7 at one minute (35.5% in Group I, 20.0% in Group II, 17.4% in Group III; P=0.010). The percentage of histologic chorioamnionitis was significantly higher in both amnionitis groups compared to Group III (67.7% in Group I, 56.0% in Group II, 4.0% in Group III; P=0.000). CONCLUSION: LEA without chorioamnionitis is not associated with maternal fever (38.0 degrees C), increased operative delivery rates or low Apgar scores.

Cardiopulmonary malformations in the inv/inv mouse.

The inv/inv mouse carries an insertional mutation in the inversin gene, (inv, for inversion of embryonic turning). Previously it had been reported that almost 100% of the homozygous offspring (inv/inv) were characterized by situs inversus totalis. In this report we identify the spectrum of cardiopulmonary anatomical abnormalities in inv/inv mice surviving to birth to determine whether the abnormalities seen are of the categories classically associated with human situs abnormalities. Stillborn mice, offspring that died unexpectedly (within 48 hr after birth), and neonates with phenotypic characteristics of situs inversus (right-sided stomachs, growth failure or jaundice) were processed for standard histological examination. Of 173 offspring, 34 (20%) neonates (11 stillborn, 9 unexpected deaths, and 14 mice with situs inversus phenotype) were examined, 27 of which were genotyped to be inv/inv. Interestingly, three inv/inv mice (11%) were found to have situs solitus. Twenty-four had situs inversus with normal, mirror-image cardiac anatomy (dextrocardia with atrioventricular concordance, ventriculoarterial concordance and a right aortic arch). The overall incidence of cardiovascular anomalies observed was 10 out of 27 (37%). The most frequent severe malformation, identified in 3 out of 27 animals, was a complex consisting of pulmonary infundibular stenosis/atresia with absence of pulmonary valve tissue and a ventricular septal defect. The pulmonary phenotype in inv/inv mice was situs inversus with occasional minor lobar abnormalities. We conclude that 1) cardiopulmonary malformations in inv/inv mice are not rare (37%), 2) the cardiopulmonary malformations observed in inv/inv specimens are not of the spectrum typically associated with human heterotaxia. In particular, inv/inv mice have a propensity for defects in the development of the right ventricular outflow tract and the interventricular septum, and 3) approximately one out of ten inv/inv mice is born with situs solitus and shows cardiac anomalies that correspond to those observed in inv/inv specimens with situs inversus. Our data therefore suggest that inversin, the product of the inv locus, may have specific roles in cardiac morphogenesis independent of its role in situs determination.

Conotruncal anomalies in the trisomy 16 mouse: an immunohistochemical analysis with emphasis on the involvement of the neural crest.

The trisomy 16 (Ts16) mouse is generally considered a model for human Down's syndrome (trisomy 21). However, many of the cardiac defects in the Ts16 mouse do not reflect the heart malformations seen in patients suffering from this chromosomal disorder. In this study we describe the conotruncal malformations in mice with trisomy 16. The development of the outflow tract was immunohistochemically studied in serially sectioned hearts from 34 normal and 26 Ts16 mouse embryos ranging from 8.5 to 14.5 embryonic days. Conotruncal malformations observed in the Ts 16 embryos included double outlet right ventricle, persistent truncus arteriosus, Tetralogy of Fallot, and right-sided aortic arch. This spectrum of malformations is remarkably similar to that seen in humans suffering from DiGeorge syndrome (DGS). As perturbation of neural crest development has been proposed in the pathogenesis of DGS we specifically focussed on the fate of neural crest derived cells during outflow tract development of the Ts16 mouse using an antibody that enabled us to trace these cells during development. Severe perturbation of the neural crest-derived cell population was observed in each trisomic specimen. The abnormalities pertained to: 1) the size of the columns of neural crest-derived cells (or prongs); 2) the spatial orientation of these prongs within the mesenchymal tissues of the outflow tract; and 3) the location in which the neural crest cells interact with the myocardium. The latter abnormality appeared to be responsible for ectopic myocardialization found in trisomic embryos. Our observations strongly suggest that abnormal neural crest cell behavior is involved in the pathogenesis of the conotruncal malformations in the Ts16 mouse.