Differences in Blood Pressure in Infants After General Anesthesia Compared to Awake Regional Anesthesia (GAS Study-A Prospective Randomized Trial).

BACKGROUND: The General Anesthesia compared to Spinal anesthesia (GAS) study is a prospective randomized, controlled, multisite, trial designed to assess the influence of general anesthesia (GA) on neurodevelopment at 5 years of age. A secondary aim obtained from the blood pressure data of the GAS trial is to compare rates of intraoperative hypotension after anesthesia and to identify risk factors for intraoperative hypotension. METHODS: A total of 722 infants ≤60 weeks postmenstrual age undergoing inguinal herniorrhaphy were randomized to either bupivacaine regional anesthesia (RA) or sevoflurane GA. Exclusion criteria included risk factors for adverse neurodevelopmental outcome and infants born at <26 weeks of gestation. Moderate hypotension was defined as mean arterial pressure measurement of <35 mm Hg. Any hypotension was defined as mean arterial pressure of <45 mm Hg. Epochs were defined as 5-minute measurement periods. The primary outcome was any measured hypotension <35 mm Hg from start of anesthesia to leaving the operating room. This analysis is reported primarily as intention to treat (ITT) and secondarily as per protocol. RESULTS: The relative risk of GA compared with RA predicting any measured hypotension of <35 mm Hg from the start of anesthesia to leaving the operating room was 2.8 (confidence interval [CI], 2.0-4.1; P < .001) by ITT analysis and 4.5 (CI, 2.7-7.4, P < .001) as per protocol analysis. In the GA group, 87% and 49%, and in the RA group, 41% and 16%, exhibited any or moderate hypotension by ITT, respectively. In multivariable modeling, group assignment (GA versus RA), weight at the time of surgery, and minimal intraoperative temperature were risk factors for hypotension. Interventions for hypotension occurred more commonly in the GA group compared with the RA group (relative risk, 2.8, 95% CI, 1.7-4.4 by ITT). CONCLUSIONS: RA reduces the incidence of hypotension and the chance of intervention to treat it compared with sevoflurane anesthesia in young infants undergoing inguinal hernia repair.

Dysrhythmias following intravenous metoclopramide.

A case is described in which administration of intravenous metoclopramide was twice followed by cardiac dysrhythmias. The literature is reviewed.

Relevance of histamine to the anaesthetist.

Histamine is a widely distributed amine with many functions, both physiological and pathological. The anaesthetist may encounter histamine in several of these roles, many of which require further elucidation. Histamine research is involved in the investigation of release mechanisms and their modification, both having implications for the clinical situation.

Basophil histamine release studies in the evaluation of a new anaesthetic agent.

Propofol (2,6-diisopropylphenol) has recently been introduced into clinical practice as an induction agent. This study evaluated the effect of propofol on basophil histamine release in 13 healthy subjects. No release was demonstrated in 11 subjects. Two subjects released histamine at the highest drug concentration, one also releasing at lower concentrations. Both subjects whose basophils released histamine in response to propofol were anaesthetists using the drug during the course of their practice.

Repeat epidural analgesia and unilateral block.

The use of epidural analgesia has become so widespread in recent years that many women are now requesting repeat epidural analgesia for their second or subsequent labour. This study examines the incidence of problems at insertion and of inadequate block in 71 multiparae having second epidurals compared with 150 primiparae having their first epidural. Unilateral block occurred in 6.66% of primiparae and 18.3% of multiparae (P < 0.02). There was no association between difficulty of insertion of catheter, blood in needle/catheter or paraesthesia and unilateral blockade. Epidurals were inserted at a greater dilatation (P < 0.05) and there was a shorter time to delivery (P < 0.01) in the multiparous group. We conclude that unilateral block is thus more common in women receiving repeat epidurals.

Histamine release during cardiopulmonary bypass in neonates and infants.

PURPOSE: Histamine release has been previously documented in adults and children during cardiopulmonary bypass (CPB). It has not been studied in neonates nor during deep hypothermic circulatory arrest (DHCA). Histamine effects could explain many perioperative complications of congenital cardiac surgery such as dysrhythmias and massive oedema. Therefore, documentation of histamine release in the perioperative period is of clinical importance. The source of histamine can be determined by measurement of tryptase which is released with histamine from mast cells but not basophils. METHODS: Blood samples for histamine and tryptase were taken before and after specific events eg. cross-clamp removal, during anaesthesia and CPB in 14 infants and seven neonates undergoing complex congenital heart repairs and were analysed by commercial radioimmunoassays. Haemodynamic variables and pre and post-op weights were recorded to look for correlation between pathophysiological events and histamine release. RESULTS: Histamine concentration decreased at the start of bypass (0.69 to 0.38 ng.ml-1 at five minutes, (P < .005). There were no changes associated with DHCA and a small rise with reventilation (P < 0.02). Histamine concentration was lower in neonates than in infants (P < 0.05) during CPB. Plasma histamine and tryptase concentrations did not correlate, suggesting histamine release was from basophils and not from mast cells. Haemodynamic variables did not correlate with histamine concentrations. CONCLUSION: There was no major histamine release during CPB in infants and neonates. There was no relationship between histamine concentrations and clinical variables. Histamine released during CPB appears to come from basophils and may be a function of age.

Management of postoperative chylothorax with nitric oxide: a case report.

OBJECTIVE: To describe the use of inhaled nitric oxide in the management of refractory postoperative chylothorax. DESIGN: Case report. SETTING: A pediatric intensive care unit of a tertiary care children's hospital. PATIENT: A neonate with refractory chylothoraces complicated by moderate pulmonary hypertension after a complicated arterial switch operation. INTERVENTIONS: Administration of inhaled nitric oxide through a ventilator circuit. MEASUREMENTS AND MAIN RESULTS: The institution of inhaled nitric oxide at 20 ppm resulted in a marked reduction in chest tube drainage and a decrease in echocardiographically estimated pulmonary artery pressure from 50%-75% systemic to 30%-50% systemic. Chest tube drainage doubled when the nitric oxide was decreased to 10 ppm and, again, dramatically decreased after raising nitric oxide back to 20 ppm. After 8 days of nitric oxide therapy, the chest tube drainage ceased. Nitric oxide therapy was successfully discontinued 19 days after initiation, with no recurrence of chylothorax. There was no effect of nitric oxide on systemic blood pressure. Methemoglobin levels while on NO remained <1.7%. CONCLUSION: Consideration may be given to the use of inhaled nitric oxide in the therapy of refractory chylothoraces complicated by central venous hypertension.

Use of adenosine in multiple doses for supraventricular tachycardia in an infant.

The treatment of recurrent supraventricular tachycardia in a 3-week-old infant is described. Multiple doses of adenosine were used successfully to convert the dysrhythmia, without adverse effects or apparent tachyphylaxis.

Histamine release during paediatric cardiopulmonary bypass.

Histamine release occurs during paediatric cardiopulmonary bypass at the time of removal of the aortic cross-clamp. Left atrial histamine levels are significantly (p less than 0.02) higher than right atrial levels at the time of reventilation of the lungs. These results suggest that histamine is released from the pulmonary vasculature following reperfusion.

Histamine release during paediatric cardiopulmonary bypass.

Histamine release is part of the general inflammatory response and occurs during surgery and cardiopulmonary bypass (CPB) in adults. Few data are available for children. Histamine release was studied in 23 children undergoing CPB with standard anaesthetic and CPB techniques. Blood sampling was performed in relation to specific anaesthetic and surgical events, e.g., start of CPB, removal of aortic clamps, reventilation of the lungs. Plasma histamine was determined by a single isotope radioenzymatic technique. There was no consistent histamine release in the study population although there was an increase in plasma histamine concentration in some subjects after initiation of CPB (P < 0.05) and on removal of the aortic cross-clamp (P < 0.05). No correlation was demonstrated between histamine concentration and systolic arterial pressure, temperature, duration of CPB or cross-clamp time. Histamine concentration was positively correlated with heart rate.

Histamine release by morphine and diamorphine in man.

Intravenous morphine and diamorphine are routinely used for postoperative analgesia but the relative histamine releasing abilities of these drugs have not been compared in man. Thirty-eight patients were randomly allocated to receive morphine (0.16 mg.kg-1) or diamorphine (0.08 mg.kg-1) after abdominal surgery. Blood samples for histamine were taken before, and at timed intervals after, opioid administration and analysed by an isotopic radioenzymatic technique. Haemodynamic parameters and pain scores were recorded before and after analgesic administration, and a series of eight basophil histamine release studies was also performed. Significant histamine release (plasma concentration > 2 ng.ml-1 or rise of > 700% baseline) occurred in 23.5% of the morphine group and 21.1% of the diamorphine group. Histamine was released earlier in those receiving diamorphine, but no significant change in haemodynamic parameters occurred, and no histamine release was demonstrated in the basophil histamine release studies. These findings suggest that morphine and diamorphine release histamine from mast cells rather than basophils.

Weaning from ventilation after cardiopulmonary bypass: evaluation of a non-invasive technique.

Weaning of patients from IPPV after cardiopulmonary bypass (CPB) is usually monitored by frequent arterial blood gas analysis. Non-invasive monitoring has the advantage of providing continuous and instantaneous information and could reduce the frequency of arterial blood gas sampling. Twenty patients were studied to determine the reliability of capnometry and pulse oximetry in this situation. The effects of hypothermia and moderate haemodynamic instability were examined. A further 40 patients were then weaned using non-invasive monitoring. Correlation between PaCO2 and PETCO2 was 0.64-0.79 for the mass spectrometer and 0.67-0.81 for the infra-red analyser. No clinical problems arose. The detection rate for mild hypercarbia was 78.6 per cent and 50 per cent for hypoxia. Possible reasons for this are discussed. Once CO2 and O2 gradients are established, pulse oximetry and capnometry provide sufficiently reliable monitoring to enable weaning from IPPV, with the advantage of continuous display, and allow a reduction in the use of arterial blood gas analyses.

Potentiation of atracurium neuromuscular blockade by enflurane: time-course of effect.

This study was designed to determine the time required for potentiation of atracurium neuromuscular blockade after the introduction of enflurane. Ten ASA physical status I and II adults anesthetized with thiopental, nitrous oxide, and alfentanil were given 0.4 mg/kg atracurium besylate. The force of contraction of the adductor pollicis muscle in response to train-of-four stimulation of the ulnar nerve was recorded. When the first twitch (T1) of the train-of-four recovered to 10% of control, an atracurium infusion was started and adjusted to keep the level of blockade constant. After 15 min of stable blockade, 1.6%-1.7% end-tidal enflurane was started and maintained for up to 2 h. Venous blood samples were drawn and plasma atracurium concentrations were measured 15 min before and 0, 5, 10, 15, 30, 45, 60, 90, and 120 min after the introduction of enflurane. Atracurium plasma concentrations were 730 +/- 127 (SEM) ng/mL at time 0. During the first 30 min, no significant decrease in plasma levels occurred; but at 45 min, concentrations were only 67% +/- 8% of their initial value (P less than 0.01) and 48% +/- 2% at 120 min (P less than 0.01). This suggests that the interaction between enflurane and atracurium is time-dependent. Clinically, the interaction between atracurium and enflurane is negligible during procedures of less than 45 min.

Basophil histamine release. A study in allergy to suxamethonium.

A patient who suffered a severe hypotensive episode after induction of anaesthesia, was subsequently found to show positive skin-test responses to suxamethonium. Investigation revealed that suxamethonium induced basophils from the patient to release histamine to an extent comparable to that found after exposure to anit-IgE. Basophils from control subjects showed no such response. Basophil histamine release may offer a useful approach to the investigation of adverse drug reactions.

Respiratory function in children during recovery from neuromuscular blockade.

Residual neuromuscular blockade is a major risk factor for respiratory insufficiency. We examined the relationship between neuromuscular and respiratory function in 18 ASA I or II children aged 2-4 years. Lung function was measured by pneumotachography and transpulmonary pressure, neuromuscular transmission by first twitch response ratio (T1:T1) and train-of-four ratio (TOFR), before and at specific points in recovery from vecuronium paralysis. The tidal volume was directly related to maximal inspiratory pressure at occlusion (PIOCC), P < 0.001, whereas the minute ventilation (VE) was related to the respiratory drive (P0.1), P < 0.001. The best predictors of minute ventilation were the P0.1 (r = 0.57), and the TOFR (r = 0.62). PIOCC and P0.1 correlated closely (r = 0.889, P = 0.002) but TOFR and T1:T1 did not correlate with either. Our results show that the occlusion pressure measurements, P0.1 and PIOCC, were good predictors of both VE.kg-1 and respiratory work.