Extracorporeal liver perfusion system for successful hepatic support pending liver regeneration or liver transplantation: a pre-clinical controlled trial.

BACKGROUND: There is a well recognized need for a system capable of providing effective support for patients with hepatic failure pending liver regeneration or liver transplantation. Recent attempts of using bioartificial liver containing encapsulated porcine hepatocytes, the deployment of emergency whole liver, or hepatocyte transplantation are complex and not consistently successful. The technique of ex vivo hepatic perfusion developed and used clinically by Abouna in the 1970s, has now been redesigned in a perfusion circuitry that mimics the physiological conditions of a normal liver. Before clinical application of this system, a preclinical trial was carried out in dogs with induced hepatic failure. METHODS: Acute hepatic failure was induced in dogs by an end-to-side porto caval shunt, followed 24 hr later, by a 2-hr occlusion of the hepatic artery. All animals (n=18) were medically supported and were divided into three groups. In the control group (n=6) only medical support was used. In the experimental group (n=12) the animals were connected to the ex vivo liver support apparatus during acute hepatic failure via an AV shunt using a dog liver (n=6) or calf liver (n=6) (after a temporary extracorporeal bovine kidney transplant to remove preformed xeno antibody). Hepatic perfusion was carried out at 37 degrees C through the hepatic artery and portal vein at physiological pressures, and blood flow rate for 6-8 hr. RESULTS: All control animals died of progressive hepatic failure at 14-19 hr after clamping the hepatic artery. The animals treated with ex vivo liver showed remarkable clinical and biochemical improvement. Five animals survived for 36-60 hr. Another seven animals recovered completely and became long-term survivors with biochemical and histological evidence of regeneration of their own liver. Biopsy of the allogeneic ex vivo liver at the end of perfusion showed some interstitial edema. Similar biopsy of the xenogeneic calf liver showed only mild and delayed xenograft rejection, which was most likely due to removal of preformed xeno antibody by temporary transplantation of the calf kidney before liver perfusion. CONCLUSIONS: The observations and results obtained in this trial strongly confirm that extracorporeal perfusion through a whole liver, using the system described, is very successful and cost effective for the treatment of acute, but reversible hepatic failure, as well as serving as a bridge to liver transplantation. The time has come for this form of liver support technology to be reintroduced and widely used.

A non-rebreathing coaxial anaesthesia system: dependence of end-tidal gas concentrations on fresh gas flow and tidal volume.

A non-rebreathing adaptation of the Bain coaxial anaesthesia circuit was developed in Nepal as a simple and economical anaesthetic system for underdeveloped countries. It was made by inserting a coaxial (Bain) tubing between an Ambu-E valve and an Ambu self-inflating bag. The present study examined the dependence of end-tidal gas concentrations on fresh gas flow and tidal volume during halothane/oxygen/air inhalation anaesthesia. Four levels of fresh gas flow with normocapnia (0.2-3 l.min-1) and three levels of tidal volume at a constant respiratory rate of 15 breath.min-1 (to achieve end-tidal carbon dioxide values of 4 +/- 0.5%, 5 +/- 0.5% and 6 +/- 0.5%) were introduced in random order. Twelve ASA class 1 and 2 adult patients having intra-abdominal or pelvic surgery were studied. With increasing fresh gas flow rates, there were proportionate increases in the end-tidal concentrations of oxygen and halothane; with decreasing tidal volume and therefore less air dilution, there were proportionate increases in the end-tidal concentrations of carbon dioxide, oxygen and halothane. Both effects were statistically and clinically significant. Thus, when this system is used as described, the end-tidal concentrations of oxygen and halothane are highly dependent upon both the fresh gas flow and the tidal volume.

The experiential curriculum: an alternate model for anaesthesia education.

The shift to direct entry into residency training from medical school for all graduates will offer new challenges for anaesthesia training programmes. In this paper we argue that it also offers us an opportunity to re-evaluate our current approach to anaesthesia education. Emphasis in the residency programmes should be to provide trainees with clinical experiences and stimulation that will develop the required traditional competencies. It should also cultivate competency in clinical decision-making, intuition and judgement. Our purpose is to generate discussion by proposing an alternate curriculum model, the experiential curriculum. The basic premise is that learning is a process and outcome is to a large extent related to what the learner does. The process begins with an experience that provides for observation and reflection. Integration of the thoughts provides the basis for executing either existing or new actions. In the experiential curriculum residency training and learning are enhanced by documenting and critically evaluating the experiences to which the resident is exposed. Included within such a structured programme are the methodologies of problem-based and evidence-based learning. Faculty development will be required to help the resident pursue these skills of self-evaluation and efficient learning. We believe that incorporation of an experiential curriculum into the residency training programme will achieve the goals listed above and allow maturation of the process of lifelong learning. It will also allow greater achievement of the application of new information to one's practice.

A modification of the Bain system for ambient air-oxygen inhalation.

In developing countries like Nepal, anaesthetic compressed gases, especially nitrous oxide, are expensive and in short supply and anaesthetic techniques must equally use oxygen and volatile anaesthetics sparingly. We have designed a non-rebreathing anaesthetic system which meets these requirements. An Ambu-E anaesthetic valve and self-inflating Ambu bag connected to a Bain system form a non-rebreathing system which uses ambient air to supplement a mixture of low flow oxygen and halothane. Over 100 patients have been anaesthetised with this system using a balanced anaesthetic technique. The oxygen flow was 2 l.min-1 and the average halothane consumption was 8 ml.h-1. The average inspired oxygen concentration was 34%, and the air:oxygen dilution ratio was 5:1. A graphical analysis of gas flow predicts that the system is almost 100% efficient, in that almost all of the oxygen and halothane will enter the alveoli. Our experience confirms that this is a safe, simple and economical method for inhalation anaesthesia. We recommend it for locations where anaesthetic machines and mechanical ventilators are lacking, and where medical oxygen is in short supply.

The postoperative interview: assessing risk factors for nausea and vomiting.

Most studies of postoperative nausea and vomiting have concentrated on single etiologic factors and have not detailed the method of assessing these symptoms. This study used postoperative interview data from patients at four teaching hospitals during 1988-89, to determine 1) risk factors for nausea/vomiting, 2) whether the type of surgery affected the rate of nausea/vomiting among female patients, 3) whether differences in rates across hospitals were due to differences in patient case-mix, and 4) whether there were differences in the rate of nausea/vomiting among the patients of individual anesthesiologists. Research nurses performed 16,000 interviews (59% of all inpatients) from a closed-question standardized format. With a multiple logistic regression that controlled simultaneously for all risk factors, factors associated with increased risk for nausea/vomiting for all patients included younger age, female, lower physical status score, no preoperative medical conditions, nonsmokers, elective procedures, longer duration of anesthesia, inhaled anesthetics, use of intraoperative opioids, and gynecologic or ophthalmologic operations. Among women, risk factors were similar, with minor gynecologic surgery associated with increased risk (relative odds = 2.30). We found marked variations in the rate of nausea/vomiting across hospitals (range, 39% to 73%), and these variations were not explained by the case-mix of patients. The rate of nausea/vomiting varied substantially across anesthesiologists in each hospital and the differences were not explained by differences in the patients they managed. Thus in the time period immediately preceding the introduction of newer antiemetic drugs, we found that the rates of this common problem were persistently high as perceived from the patients' point of view.

A comparative study of the efficacy of postoperative analgesia with intraoperative epidural lidocaine with or without morphine.

We compared postoperative analgesia in 15 patients (group A) who were given intraoperative epidural morphine 3 mg and lidocaine 150 mg after laminectomy/discectomy with that of 15 patients (group B) who were given only epidural lidocaine 150 mg. Epidural administration was accomplished by direct placement of the epidural catheter into the epidural space under direct vision during surgery. Eight patients (53%) in group A and 15 patients (100%) in group B required supplementary narcotics during the first 24 h postoperatively (P<0.05). The amount of supplementary narcotics given to group A patients was significantly less than that for group B (P<0.05), and the pain scores for group A patients were also significantly lower at 1, 2, and 6 h postoperatively (P<0.05). There was no difference in the observed side effects in the two groups. We conclude that postoperative pain relief following laminectomy/discectomy is superior when epidural morphine is added to lidocaine than when lidocaine is being used alone.

Tidal volume, lung hyperinflation and arterial oxygenation during general anaesthesia.

Impaired pulmonary oxygen (O2) exchange is common during general anaesthesia but there is no clinical unanimity as to methods of prevention or treatment. We studied 14 patients at risk for pulmonary dysfunction because of increased age, obesity, cigarette smoking, or chronic lung disease. Pulmonary O2 exchange was measured during four conditions of ventilation: awake spontaneous, conventional tidal volume (CVT, 7 ml.kg-1) or high tidal volume (HVT, 12 ml.kg-1) controlled ventilation, and five min after manual hyperinflation (HI) of the lungs. The FIO2 was controlled at 0.5, and FETCO2 was kept constant by adding dead space during HVT. Eight patients were ventilated with N2O/O2 and six with air/O2. Arterial blood gases were used to calculate the (A-a)DO2. In seven patients (A-a)DO2 worsened after induction of anaesthesia, while in seven there was no change or an improvement. Manual HI significantly reduced (A-a)DO2, but changing tidal volume (VT) had no effect. Using a multivariate model to predict O2 exchange, obesity and type of surgery were significantly associated with worsening, while level of VT and inspiratory gas (N2O or N2) were not significant predictors. Thus patient and surgical factors were more important determinants of pulmonary gas exchange during anaesthesia than were tidal volume or inspiratory gas. Manual HI is a simple and effective manoeuvre to improve gas exchange.

Fresh gas flow and carbon dioxide rebreathing in a low pressure semi-open anaesthesia system.

We have constructed a simple system for field anaesthesia by using a Farman entrainer and a semi-open circuit to convert a draw-over apparatus to a continuous flow air/O2 system. Compressed O2 was the driving gas for the entrainer; fresh gas (FG) delivered to the semi-open circuit was a mixture of O2, entrained air and anaesthetic vapour. The purpose of this study was to examine FG flow rate and CO2 rebreathing during intermittent positive pressure ventilation (IPPV). A non-rebreathing inflation valve (Laerdal) placed at the end of the expiratory (efferent) limb of the circuit vented both expiratory gas and excess FG. Ambient air IPPV was applied through the Laerdal valve from a self-inflating bag or ventilator. Since this circuit is functionally similar to a T-piece, the gas from the efferent limb (340 ml, containing FG) entered the lungs first. If tidal volume was larger than 340 ml the balance was ambient air. Minute ventilation of the lungs with efferent limb gas was defined as Veff. Respiratory gas was sampled at the endotracheal tube and the CO2 tension was measured with a NIHON-KOHDEN CO2 analyzer. Thirty-seven adult patients having intra-abdominal or pelvic surgery under general tracheal anaesthesia were studied. Four FG flow rates (5.7, 8.0, 9.3, and 10.4 L.min-1), corresponding to driving gas pressures of 40, 60, 80, and 100 mmHg, were introduced in random order. Although inspired CO2 was detected at FG flow rates of 5.7-9.3 L.min-1, there were no differences in PETCO2 among the four groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaesthesia services and the education of anaesthetists in Nepal: a model for sustainable development?

In 1985 the University of Calgary in Canada and Tribhuvan University in Kathmandu, Nepal Jointly established the Diploma in Anaesthesiology (DA) programme in Nepal. To evaluate the impact of the DA Programme and provide a data base for long-term planning we conducted a national survey in 1992. We sought to describe anaesthesia manpower and workloads, and to make an inventory of facilities, equipment, and supplies in different sized hospitals. Twenty-seven hospitals providing surgical services were included, nine inside and 18 outside the Kathmandu valley. Seventeen of the 21 respondent hospitals had at least one specialist anaesthetist. The results identify both strengths and weaknesses in Nepal's anaesthesia services and provide important guidelines for planning. When the DA course was launched there were only seven specialist anaesthetists in Nepal. The shortage of anaesthetists was an important factor limiting surgical services, and after DA graduates were posted to zonal (50 bed) and regional (150-200 bed) hospitals the surgical case loads doubled. There are now about 40 specialist anaesthetists in the country, of which half are DA graduates, but many hospitals have only one anaesthetist. That isolation, plus lack of continuing education (CME), are important factors threatening quality of care. Recognizing the singular role of the DA programme in alleviating Nepal's shortage of anaesthetists, we conclude that it should be renewed and strengthened to meet the needs of the next decade. Techniques commonly used at the zonal level: regional, draw-over, and total IV anaesthesia, should be stressed. At the same time fresh initiatives are required in CME and higher education for the renewal of teaching staff.(ABSTRACT TRUNCATED AT 250 WORDS)

Pressure controlled-inverse ratio ventilation and pulmonary gas exchange during lower abdominal surgery.

Although pressure controlled-inverse ratio ventilation (PC-IRV) has been used successfully in the treatment of respiratory failure, it has not been applied to the treatment of respiratory dysfunction during anaesthesia. With PC-IRV the inspiratory wave form is fundamentally altered so that inspiratory time is prolonged (inverse I:E), inspiratory flow rate is low, and the peak inspiratory pressure is limited. Positive end-expiratory pressure (PEEP) can be applied and the mean airway pressure is higher than with conventional ventilation. To assess the clinical efficacy of this new mode of ventilation we studied ten patients having lower abdominal gynaecologic surgery in the Trendelenburg position under general anaesthesia. Pulmonary O2 exchange was determined during four steady states: awake control (AC), after 30 and 60 min of PC-IRV during surgery, and at the end of surgery. Patients' lungs were ventilated with air/O2 by a Siemens 900C servo ventilator in the PC-IRV mode with an I:E ratio of 2:1 and 5 cm H2O of PEEP. The FIO2 was controlled at 0.5 and arterial blood gases were used to calculate the oxygen tension-based indices of gas exchange. There were significant increases of (A-a) DO2 at 30 and 60 min (41 and 43%). These changes were less than those reported in a previous study using conventional tidal volume ventilation (7.5 ml.kg-1) and were similar to those in patients whose lungs were ventilated with high tidal volumes (12.7 ml.kg-1). Thus, in this clinical model of compromised gas exchange, arterial oxygenation was better with PC-IRV than with conventional ventilation, but not better than with large tidal volume ventilation.

Obstetric admissions to the intensive care unit--a retrospective review.

A five-year retrospective study of obstetric admissions to the Surgical Intensive Care Unit (SICU) in the National University Hospital, Singapore was carried out with the aim of determining the incidence, causes and outcome of these admissions. Most of the patients were admitted following emergency caesarean sections. Obstetric complications was the reason for admission in 56.8% with hypertensive disease of pregnancy being the major cause and haemorrhage accounting for the rest. Anaesthetic complications accounted for 21.6% of admissions and these included difficult intubation, aspiration pneumonitis, cardiac arrhythmias and respiratory depression. Medical complications due to cardiovascular disease, autoimmune disease and malignancy also accounted for 21.6% of admissions. Only 37 out of 16264 deliveries (0.22%) required intensive care support. The median of duration of stay was one day.

Carbon dioxide absorption and gas exchange during pelvic laparoscopy.

Twelve ASA physical status I-II patients undergoing pelvic laparoscopy for infertility were enrolled in a study to quantify the effects of CO2 insufflation and the Trendelenburg position on CO2 elimination and pulmonary gas exchange, and to determine the minute ventilation required to maintain normocapnia during CO2 insufflation. Measurements of O2 uptake (VO2), CO2 elimination (VCO2), minute ventilation (VE), FIO2, and respiratory exchange ratio (RQ) were made during three steady states: control (C) taken after 15 min of normoventilation but before CO2 insufflation, after 15 min (L1) and 30 min (L2) of hyperventilation during CO2 insufflation. The FIO2 was controlled at 0.5 and arterial blood gases were used to calculate the oxygen tension-based indices of pulmonary gas exchange. After 15 min and 30 min of CO2 insufflation, the volume of CO2 absorbed from the peritoneal cavity was estimated at 42.1 +/- 5.1 and 38.6 +/- 6.6 (SEM) ml.min-1 respectively, increasing CO2 elimination through the lungs by about 30%. Hyperventilation of the lungs by a 20-30% increase in minute ventilation maintained normocapnia. Despite the CO2 pneumoperitoneum and Trendelenburg position, there was no impairment of pulmonary oxygen exchange as estimated by (A-alpha)DO2. This study demonstrated that a 30% increase in minute ventilation, achieved by increasing tidal volume to more than 10 ml.kg-1, is sufficient to eliminate the increased CO2 load and maintain normal pulmonary O2 exchange during pelvic laparoscopy.

Oxygen consumption and carbon dioxide elimination after release of unilateral lower limb pneumatic tourniquets.

Oxygen consumption (VO2), carbon dioxide elimination (VCO2), and respiratory exchange ratio (RQ) were continuously measured in 15 male and 15 female adults during knee surgery, with the leg exsanguinated by an inflatable tourniquet around the thigh. Arterial blood was also intermittently sampled for blood gas analysis, electrolytes, and lactate content before and after tourniquet deflation. There was a significant increase in VO2 and VCO2 after tourniquet deflation, which was more pronounced in the male (aged 29.5 +/- 14.8 yr, mean +/- SD) than the female (aged 56.9 +/- 15.6 yr) patients, both in terms of maximal increase (P less than 0.001) and percent of increase from values before deflation (P less than 0.001 and P = 0.01). The body weights and tourniquet inflation times were not significantly different between the male and female patients. Excess VO2 (O2 debt) and excess VCO2 over 12 min after deflation of the tourniquet were also significantly higher for male (593.5 +/- 222.9 mL and 714.9 +/- 463.8 mL, respectively) than for female patients (302 +/- 73.3 mL and 196 +/- 162.22 mL, respectively; P less than 0.01). There was no correlation between the duration of tourniquet inflation time and peak increase in VO2, peak increase in VCO2, and O2 debt over 12 min after deflation of the tourniquet; however, tourniquet time was weakly correlated with excess VCO2 over 12 min after tourniquet deflation (r = 0.55, P = 0.002). There was a significant decrease in pHa (P less than 0.001) from release of PaCO2 and lactate after tourniquet deflation. Plasma potassium levels also increased significantly after tourniquet release (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

The Canadian four-centre study of anaesthetic outcomes: III. Are anaesthetic complications predictable in day surgical practice?

To understand better the factors important to the safety of anaesthesia provided for day surgical procedures, we analyzed the intraoperative and immediate postoperative course of patients at four Canadian teaching hospitals' day treatment centres. After excluding those who received only monitored anaesthesia care, there were 6,914 adult (non-obstetrical) patients seen over a twelve-month period in 1988-89. The rate of adverse outcome consequent to their care was identified by a comprehensive surveillance system which included review of anaesthetic records (four hospitals) and follow-up telephone calls (two hospitals). The relationship between adverse events and preoperative factors was determined by using a multiple logistic regression analysis that included age, sex, duration of the procedure and the hospital care. There were no deaths during the study period and major morbid events were infrequent. Patient preoperative disease was predictive of some intraoperative events relating to the same organ system, but not to events in the PACU. Some unexpected relationships emerged including preoperative hypertension being related to a greater risk of difficult intubation, and neurological disease to perioperative cardiac abnormalities. Patients judged obese, or inadequately fasted, were found to experience a greater rate of recovery problems as well as discomfort. While the low response rate (36%) to the telephone interviews created a sampling bias, the high rate of patient dissatisfaction among those reached is disconcerting. We conclude that day surgical patients with preoperative medical conditions, even when optimally managed, are at higher risk for adverse events in the perioperative period.

The Canadian four-centre study of anaesthetic outcomes: II. Can outcomes be used to assess the quality of anaesthesia care?

Since anaesthesia, unlike medical or surgical specialties, does not constitute treatment, this study sought to determine if methods used to assess medical or surgical outcomes (that is the determination of adverse outcome) are applicable to anaesthesia. Anaesthetists collected information on patient, surgical and anaesthetic factors while data on recovery room and postoperative events were evaluated by research nurses. Data on 27,184 inpatients were collected and the analysis of outcomes determined for the intraoperative, post-anaesthetic care unit and postoperative time periods. Logistic regression was used to control for differences in patient populations across the four hospitals. In addition, a random selection of 115 major events was classified by a panel of anaesthetists into anaesthesia, surgical and patient-disease contributions. Across the three time periods, large variations in minor outcomes were found across the four hospitals; these variations ranged from two- to five-fold after case-mix adjustment (age, physical status, sex, emergency versus elective and length of anaesthesia). The rates of major events and deaths were similar across three hospitals; one hospital had a lower mortality rate (P less than 0.001) but had a higher rate of all major events (P less than 0.0001). Of major events assessed by physician panels, 18.3% had some anaesthetic involvement and no deaths were attributable partially or wholly to anaesthesia. Possible reasons to account for these variations in outcome include compliance in recording events, inadequate case-mix adjustment, differences in interpretation of the variables (despite guidelines) and institutional differences in monitoring, charting and observation protocols. The authors conclude that measuring quality of care in anaesthesia by comparing major outcomes is unsatisfactory since the contribution of anaesthesia to perioperative outcomes is uncertain and that variations may be explained by institutional differences which are beyond the control of the anaesthetist. It is suggested that minor adverse events, particularly those of concern to the patient, should be the next focus for quality improvement in anaesthesia.

The Canadian four-centre study of anaesthetic outcomes: I. Description of methods and populations.

The objectives of this study were first to develop and institute a methodology for the study of anaesthetic outcome for parallel use in four teaching hospitals in Canada and second, to compare rates of morbidity and mortality associated with anaesthesia between the four centres. The basic design of the study was occurrence screening with anaesthetists entering data on patient demographics, anaesthetic and surgical factors. Research nurses reviewed anaesthetic records and hospital charts and interviewed patients postoperatively. Data on 37,665 anaesthetics were collected during 1988-89 in the four teaching centres. There were major differences found across the hospitals, particularly with regard to volume, patient case-mix, anaesthetic drugs and monitoring used. The use of parallel training, repeated consultations and use of rounds and inservices contributed to the reliability and validity of the data collection. We conclude that outcome surveillance can be instituted in different hospital Departments of Anaesthesia with sufficient confidence to form the basis of comparison of anaesthetic outcome.

Efficacy of lignocaine in alleviating potassium chloride infusion pain.

A double-blind study was set up to investigate the effect of pretreatment with lignocaine on the incidence of potassium chloride infusion pain. Twenty-eight patients were randomly allocated into two equal groups. Patients in both groups were hypokalaemic and were scheduled for replacement consisting of potassium chloride 20 mmol diluted to 100 ml in dextrose 5% solution administered over two hours. Group A (lignocaine) patients were pretreated with a bolus dose lignocaine 3 ml 1%, Group B (control) received isotonic saline 3 ml. The incidence of potassium chloride infusion pain was significantly reduced in Group A. There was no adverse effect reported. This study demonstrates the efficacy of bolus dose of lignocaine in alleviating injection pain for the duration of a two-hour continuous infusion.