SummaryWe present a series of three children with sickle cell disease aged 3 months, 3 weeks and 18 months, all presenting for cardiac surgery requiring cardiopulmonary bypass. The cardiac lesions were atrioventricular septal defect, transposition of the great arteries and ventricular septal defect, with sickle cell loads of 35%, 11% and 39% respectively at presentation. We calculated that the bypass circuit would provide sufficient volume to decrease sickle cell levels to safe values, so we decided to proceed to bypass without pre-operative exchange transfusion, and modified the bypass technique so as to avoid the likely stimulants of a sickle cell crisis. Haemoglobin S levels after the start of bypass were significantly lower than before bypass, and remained low throughout the case and into the second postoperative day. By adopting this approach, we feel that we achieved a successful outcome with minimal distress to the children and their families.

This study aimed to develop a reproducible model of phosgene-induced lung injury in the pig to facilitate the future development of therapeutic strategies. Ten female young adult large white pigs were used. Following induction of anaesthesia using a halothane/oxygen/nitrous oxide mixture, arterial and venous catheters were inserted together with a pulmonary artery thermodilution catheter, and a suprapubic urinary catheter by laparotomy. Anaesthesia was maintained throughout the experiment by intravenous infusion of ketamine, midazolam and alfentanil. On completion of surgery the animals were allowed to equilibrate for 1 h and then were divided into two groups. Group 1 (n = 5) was exposed to phosgene for 10 min (mean Ct = 2443 +/- 35 mg min m(-3)) while spontaneously breathing, whereas control animals (Group 2 n = 5) were exposed to air. At 30 min post-exposure, anaesthesia was deepened in order to allow the initiation of intermittent positive pressure ventilation and the animals were monitored for up to 24 h. Cardiovascular and respiratory parameters were monitored every 30 min and blood samples were taken for arterial and mixed venous blood gas analysis and clinical chemistry. A detailed post-mortem and histopathology was carried out on all animals following death or euthanasia at the end of the 24-h monitoring period. Control animals (Group 2) all survived until the end of the 24-h monitoring period with normal pathophysiological parameters. Histopathology showed only minimal passive congestion of the lung. Following exposure to phosgene (Group 1) there was one survivor to 24 h, with the remainder dying between 16.5 and 23 h (mean = 20 h). Histopathology from these animals showed areas of widespread pulmonary oedema, petechial haemorrhage and bronchial epithelial necrosis. There was also a significant increase in lung wet weight/body weight ratio (P < 0.001). During and immediately following exposure, a transient decrease in oxygen saturation and stroke volume index was observed. From 6 h there were significant decreases in arterial pH (P < 0.01), P(a)O(2) (P < 0.01) and lung compliance (P < 0.01), whereas oxygen delivery and consumption was reduced from 15 h onwards in phosgene-exposed animals. Mean pulmonary artery pressure of phosgene-exposed animals was increased from 15 h post-exposure, with periods of increased pulmonary vascular resistance index being recorded from 9 h onwards. We have developed a reproducible model of phosgene-induced lung injury in the anaesthetized pig. We have followed changes in cardiovascular and pulmonary dynamics for up to 24 h after exposure in order to demonstrate evidence of primary acute lung injury from 16 h post-exposure. Histopathology showed evidence of widespread damage to the lung and there was also a significant increase in lung wet weight/body weight ratio (P < 0.001).

Phosgene is a chemical widely used in the plastics industry and has been used in warfare. It produces a life-threatening pulmonary edema within hours of exposure, to which no specific antidote exists. This study aims to examine the pathophysiological changes seen with low tidal volume ventilation (protective ventilation (PV)) strategies compared to conventional ventilation (CV), in a model of phosgene-induced acute lung injury. Anesthetized pigs were instrumented and exposed to phosgene (concentration x time (Ct), 2,350 mg x min x m(-3)) and then ventilated with intermittent positive pressure ventilation (tidal volume (TV) = 10 ml x kg(-1); positive end expiratory pressure, 3 cm H2O; frequency, 20 breaths x min(-1); fractional concentration of inspired oxygen, 0.24), monitored for 6 hours after exposure, and then randomized into treatment groups: CV, PV (A) or (B) (TV, 8 or 6 ml x kg(-1); positive end expiratory pressure, 8 cm H2O; frequency, 20 or 25 breaths x min(-1); fractional concentration of inspired oxygen, 0.4). Pathophysiological parameters were measured for up to 24 hours. The results show that PV resulted in improved oxygenation, decreased shunt fraction, and mortality, with all animals surviving to 24 hours compared to only three of the CV animals. Microscopy confirmed reduced hemorrhage, neutrophilic infiltration, and intra-alveolar edema.

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Inhalation of nitric oxide (NO) results in selective pulmonary vasodilation, which may be beneficial in the treatment of acute lung injury. However, NO has toxic effects, and it is important to monitor the effects and fate of inhaled NO. Under intravenous general anesthesia, large white female pigs were instrumented, ventilated with intermittent positive pressure ventilation (IPPV, FiO(2) 0.3; TV 10 ml kg(-1); RR 20 bpm; PEEP 3 cm H(2)O) and monitored for 24 h. Following a period of stabilization, groups were exposed to air (control), or to 10, 40, or 80 ppm NO, delivered via the endotracheal tube in each inspiratory breath. At regular intervals throughout the 24-h period, physiological measurements and arterial blood, plasma, and urine samples were collected. Inhalation of NO acted specifically on the pulmonary vasculature, as no alterations in systemic blood pressure were observed. Administration of NO at 80 ppm resulted in a decreased mean pulmonary artery pressure, decreased pulmonary wedge pressure, and increased methemoglobin and plasma/urine nitrate levels. At post mortem, congestion of the alveolar capillary network was noted in this group. In addition increases in plasma/urine nitrate levels were also observed in the 40 ppm group. In contrast, no significant alterations were observed in the 10 ppm group, compared to the control group. Therefore, 10 ppm inhaled NO is a dose that induced no pathological changes in normal healthy lungs and may be of use as a therapeutic adjunct in the management of acute lung injury.

A patient developed anaphylaxis during anaesthesia, towards the end of surgery, 30 s after intravenous administration of neostigmine. Anaphylaxis to neostigmine was con®rmed by demonstrating an elevated mast cell tryptase and a strongly/positive skin prick test, showing the presence of drug-speci®c IgE (skin prick tests to neostigmine were negative in normal subjects). This is a rare cause of anaphylaxis during anaesthesia.

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