Gabrielle C. Musk

Target-controlled infusion of propofol in dogs - evaluation of four targets for induction of anaesthesia

Four groups of 20 dogs were anaesthetised by means of target-controlled infusions of propofol designed to achieve 2·5 µg/ml, 3·0 µg/ml, 3·5 µg/ml or 4·0 µg/ml of propofol in blood. The dogs’ pulse rate and respiratory rate were recorded before premedication and induction, immediately after endotracheal intubation and three and five minutes later (times 0, 3 and 5, respectively), and their arterial blood pressure was recorded oscillometrically just before induction and at times 0, 3 and 5. The targets of 2·5, 3·0, 3·5 and 4·0 µg/ml resulted in the successful induction of anaesthesia in 13 (65 per cent), 16 (80 per cent), 20 (100 per cent) and 20 (100 per cent) of the dogs, respectively. The incidence of postinduction apnoea was 0 (0 per cent), one (5 per cent), two (10 per cent) and eight (40 per cent) at time 5 for groups 2·5, 3·0, 3·5 and 4·0 µg/ml, respectively, and its incidence at time 5 was significantly higher in the 4·0 µg/ml group (P<0·05) than in the other groups. In all the groups there was a significant (P<0·05) decrease in blood pressure between just before induction and the later measurements. Although there were no statistically significant differences between the groups in terms of inducing anaesthesia at a specific target, a target of 3·5 µg/ml appears to ensure a successful induction of anaesthesia without a significant increase in the incidence of apnoea.

The 'Effects of Transfusion Thresholds on Neurocognitive Outcome of Extremely Low Birth-Weight Infants (ETTNO)' Study: Background Aims, and Study Protocol

Background: Infants with extremely low birth weight uniformly develop anemia of prematurity and frequently require red blood cell transfusions (RBCTs). Although RBCT is widely practiced, the indications remain controversial in the absence of conclusive data on the long-term effects of RBCT. Objectives: To summarize the current equipoise and to outline the study protocol of the ‘Effects of Transfusion Thresholds on Neurocognitive Outcome of extremely low birth-weight infants (ETTNO)’ study. Methods: Review of the literature and design of a large pragmatic randomized controlled trial of restrictive versus liberal RBCT guidelines enrolling 920 infants with birth weights of 400–999 g with long-term neurodevelopmental follow-up. Results and Conclusions: The results of ETTNO will provide definite data about the efficacy and safety of restrictive versus liberal RBCT guidelines in very preterm infants.

Commonly applied positive end-expiratory pressures do not prevent functional residual capacity decline in the setting of intra-abdominal hypertension: a pig model

IntroductionIntra-abdominal hypertension is common in critically ill patients and is associated with increased morbidity and mortality. The optimal ventilation strategy remains unclear in these patients. We examined the effect of positive end-expiratory pressures (PEEP) on functional residual capacity (FRC) and oxygen delivery in a pig model of intra-abdominal hypertension.MethodsThirteen adult pigs received standardised anaesthesia and ventilation. We randomised three levels of intra-abdominal pressure (3 mmHg (baseline), 18 mmHg, and 26 mmHg) and four commonly applied levels of PEEP (5, 8, 12 and 15 cmH2O). Intra-abdominal pressures were generated by inflating an intra-abdominal balloon. We measured intra-abdominal (bladder) pressure, functional residual capacity, cardiac output, haemoglobin and oxygen saturation, and calculated oxygen delivery.ResultsRaised intra-abdominal pressure decreased FRC but did not change cardiac output. PEEP increased FRC at baseline intra-abdominal pressure. The decline in FRC with raised intra-abdominal pressure was partly reversed by PEEP at 18 mmHg intra-abdominal pressure and not at all at 26 mmHg intra-abdominal pressure. PEEP significantly decreased cardiac output and oxygen delivery at baseline and at 26 mmHg intra-abdominal pressure but not at 18 mmHg intra-abdominal pressure.ConclusionsIn a pig model of intra-abdominal hypertension, PEEP up to 15 cmH2O did not prevent the FRC decline caused by intra-abdominal hypertension and was associated with reduced oxygen delivery as a consequence of reduced cardiac output. This implies that PEEP levels inferior to the corresponding intra-abdominal pressures cannot be recommended to prevent FRC decline in the setting of intra-abdominal hypertension.

Clinical evaluation of alfaxalone to induce and maintain anaesthesia in cats undergoing neutering procedures

This study looked at the use and efficacy of alfaxalone for total intravenous anaesthesia (TIVA) in cats. Following intramuscular medetomidine (20 μg/kg) and morphine (0.3 mg/kg) premedication, anaesthesia was induced and maintained with intravenous alfaxalone. Patients were breathing 100% oxygen. Heart rate (HR), respiratory rate (RR), end-tidal carbon dioxide, oxygen saturation of haemoglobin and indirect arterial blood pressure via Doppler (DAP) were recorded every 5 mins. Thirty-four cats (10 males and 24 females), between the age of 6 and 18 months, and weighing between 1.8 and 5.3 kg, and undergoing neutering procedures were included in this study. The results are presented as median (min, max) values. The time to first spontaneous movement (TS) was >30 mins in 19 cats, of which 12 received atipamezole for reversal of the effects of medetomidine. The TS was 53 (43, 130) mins in these 12 cats and 50 (40, 72) mins in the other seven cats. The body temperature in those 19 cats was significantly lower than the other cats (P = 0.05). The alfaxalone induction dose and maintenance infusion rate were1.7 (0.7, 3.0) mg/kg and 0.18 (0.06, 0.25) mg/kg/min, respectively. The HR, RR and DAP were 145 (68, 235) beats/min, 17 (5, 40) breaths/min and 110 (58, 210) mmHg, respectively. Apnoea was not observed in any cat. In conclusion, alfaxalone TIVA in combination with medetomidine and morphine premedication was effective in feral and domestic cats for the performance of neutering surgery; low body temperature might have resulted in longer recoveries in some cats.

Laparoscopic surgery for orthotopic kidney transplant in the pig model.

BACKGROUND Laparoscopic surgery has become the preferred approach in surgical practice due to multiple benefits. Over the last decade, kidney transplant by laparoscopic or robotic techniques have been explored. The aim of this study is to establish a new laparoscopic technique for kidney orthotopic transplant. MATERIALS AND METHODS The study was approved by the Animal Ethics Committee of the University. Ten live female pigs (Sus scrofa), weighing 45-50 kg, underwent laparoscopic kidney orthotopic transplant on left side under general anesthesia, and the opposite right kidney was defunctioned by complete ligation of the ureter at the same time. RESULTS The vital signs of all pigs were stable during the surgery and postoperative period. There were no intraoperative complications and no conversion to open surgery. The laparoscopic kidney transplant was successful in seven of 10 pigs. Seven pigs were observed up to 4 wk as planned in the study. DISCUSSION To our knowledge, this is the first study of laparoscopic kidney orthotopic transplant in pig model with satisfactory immediate graft function. It was demonstrated that laparoscopic kidney transplant is a feasible, reliable, and safe procedure. However, it is a very demanding technique. Adequate training is mandatory for performing laparoscopic kidney transplant. This study could be used as a training model for surgeons who wish to perform human laparoscopic kidney transplant in the future.

Repeated exposure to intra-amniotic LPS partially protects against adverse effects of intravenous LPS in preterm lambs

Histologic chorioamnionitis, frequently associated with preterm births and adverse outcomes, results in prolonged exposure of preterm fetuses to infectious agents and pro-inflammatory mediators, such as LPS. Endotoxin tolerance-type effects were demonstrated in fetal sheep following repetitive systemic or intra-amniotic (i.a.) exposures to LPS, suggesting that i.a. LPS exposure would cause endotoxin tolerance to a postnatal systemic dose of LPS in preterm sheep. In this study, randomized pregnant ewes received either two i.a. injections of LPS or saline prior to preterm delivery. Following operative delivery, the lambs were treated with surfactant, ventilated, and randomized to receive either i.v. LPS or saline at 30 min of age. Physiologic variables and indicators of systemic and lung inflammation were measured. Intravenous LPS decreased blood neutrophils and platelets values following i.a. saline compared to that after i.a. LPS. Intra-amniotic LPS prevented blood pressure from decreasing following the i.v. LPS, but also caused an increased oxygen index. Intra-amniotic LPS did not cause endotoxin tolerance as assessed by cytokine expression in the liver, lung or plasma, but increased myeloperoxidase-positive cells in the lung. The different compartments of exposure to LPS (i.a. vs i.v.) are unique to the fetal to newborn transition. Intra-amniotic LPS incompletely tolerized fetal lambs to postnatal i.v. LPS.

The role of femoral venous pressure and femoral venous oxygen saturation in the setting of intra-abdominal hypertension: a pig model

Femoral venous access is frequently used in critically ill patients. Because raised intra-abdominal pressure (IAP) is also frequently found in this group of patients, we examined the impact of IAP and positive end-expiratory pressure (PEEP) on femoral venous pressure (FVP) and femoral venous oxygen saturation (Sfvo2) in an animal model. Thirteen adult pigs received standardized anesthesia and ventilation. Randomized levels of IAP (3 [baseline], 18, and 26 mmHg) were applied, with levels of PEEP (5, 8, 12, and 15 cmH2O) applied randomly at each IAP level. We measured bladder pressure (IAP), superior vena cava pressure, pulmonary artery pressure, pulmonary artery occlusion pressure, FVP, mixed venous oxygen saturation (Svo2), and Sfvo2. We found that FVP correlated well with IAP (FVP = 4.1 + [0.12 × PEEP] + [1.00 × IAP]; R2 = 0.89, P < 0.001) with a moderate bias and precision of 5.0 and 3.8 mmHg, respectively. Because the level of agreement did not meet the recommendations of the World Society of Abdominal Compartment Syndrome, FVP cannot currently be recommended to measure IAP, and further clinical trials are warranted. However, a raised FVP should prompt the measurement of the bladder pressure. Femoral venous oxygen saturation did correlate neither with Svo2 nor with abdominal perfusion pressure. Therefore, Sfvo2 is of no clinical use in the setting of raised IAP.

High Positive End-Expiratory Pressure During High-Frequency Jet Ventilation Improves Oxygenation and Ventilation in Preterm Lambs

Increasing positive end-expiratory pressure (PEEP) is advocated to recruit alveoli during high-frequency jet ventilation (HFJV), but its effect on cardiopulmonary physiology and lung injury is poorly documented. We hypothesized that high PEEP would recruit alveoli and reduce lung injury but compromise pulmonary blood flow (PBF). Preterm lambs of anesthetized ewes were instrumented, intubated, and delivered by cesarean section after instillation of surfactant. HFJV was commenced with a PEEP of 5 cm H2O. Lambs were allocated randomly at delivery to remain on constant PEEP (PEEPconst, n = 6) or to recruitment via stepwise adjustments in PEEP (PEEPadj, n = 6) to 12 cm H2O then back to 8 cm H2O over the initial 60 min. PBF was measured continuously while ventilatory parameters and arterial blood gases were measured at intervals. At postmortem, in situ pressure-volume deflation curves were recorded, and bronchoalveolar lavage fluid and lung tissue were obtained to assess inflammation. PEEPadj lambs had lower pressure amplitude, fractional inspired oxygen concentration, oxygenation index, and PBF and more compliant lungs. Inflammatory markers were lower in the PEEPadj group. Adjusted PEEP during HFJV improves oxygenation and lung compliance and reduces ventilator requirements despite reducing pulmonary perfusion.

Intraperitoneal medetomidine: a novel analgesic strategy for postoperative pain management in pregnant sheep

The absorption of medetomidine released by continuous infusion from an osmotic pump in the abdominal cavity was studied in pregnant sheep during the 24 h postoperative period. Additionally pain and sedation was assessed. Eleven sheep were studied: six were treated with a medetomidine loaded osmotic pump delivering 10 μL/h (3 μg/kg/h medetomidine); and five with a saline loaded osmotic pump (control). Serial blood samples were taken and analysed to determine plasma medetomidine levels. Medetomidine was absorbed from the peritoneal cavity and a steady plasma concentration was achieved within 10 h, mean (SD) peak concentration was 2.87 (0.22) ng/mL. Sheep receiving medetomidine analgesia had significantly lower pain scores at 10 h than controls. Four control sheep required rescue analgesia, compared with 0 in the treatment group. Delivery of 3 μg/kg/h medetomidine by an intraperitoneal osmotic pump to pregnant sheep in the 24 h postoperative period provides adequate plasma concentrations of medetomidine for analgesia without sedation.

Ex-Vivo Uterine Environment (EVE) Therapy Induced Limited Fetal Inflammation in a Premature Lamb Model.

Introduction Ex-vivo uterine environment (EVE) therapy uses an artificial placenta to provide gas exchange and nutrient delivery to a fetus submerged in an amniotic fluid bath. Development of EVE may allow us to treat very premature neonates without mechanical ventilation. Meanwhile, elevations in fetal inflammation are associated with adverse neonatal outcomes. In the present study, we analysed fetal survival, inflammation and pulmonary maturation in preterm lambs maintained on EVE therapy using a parallelised umbilical circuit system with a low priming volume. Methods Ewes underwent surgical delivery at 115 days of gestation (term is 150 days), and fetuses were transferred to EVE therapy (EVE group; n = 5). Physiological parameters were continuously monitored; fetal blood samples were intermittently obtained to assess wellbeing and targeted to reference range values for 2 days. Age-matched animals (Control group; n = 6) were surgically delivered at 117 days of gestation. Fetal blood and tissue samples were analysed and compared between the two groups. Results Fetal survival time in the EVE group was 27.0 ± 15.5 (group mean ± SD) hours. Only one fetus completed the pre-determined study period with optimal physiological parameters, while the other 4 animals demonstrated physiological deterioration or death prior to the pre-determined study end point. Significant elevations (p<0.05) in: i) inflammatory proteins in fetal plasma; ii) selected cytokine/chemokine mRNA expression levels in fetal tissues; and iii) histological inflammatory score in fetal lung, were observed in the EVE group compared to the Control group. There was no significant difference (p>0.05) in surfactant protein mRNA expression level between the two groups. Conclusion In this study, we achieved limited fetal survival using EVE therapy. Despite this, EVE therapy only induced a modest fetal inflammatory response and did not promote lung maturation. These data provide additional insight into markers of treatment efficacy for the assessment of future studies.