Metabolic acidosis and cardiopulmonary bypass: hypoperfusion or iatrogenic?

Many patients develop, to a varying extent, a metabolic acidosis during cardiopulmonary bypass (CPB). Often this acidosis is assumed to be the result of tissue hypoperfusion. However, fluids administered to patients before and during CPB, through their effects upon the strong ion difference (SID), may cause metabolic acidosis [1,2]. These fluids may also produce acidosis by haemodilution because of the decrease in plasma protein concentration [2]. The aim of this study was to determine whether metabolic acidosis occurring during CPB is the result of hypoperfusion or is iatrogenic.

Methods: Forty-nine adult patients undergoing cardiac surgery with CPB were studied. Arterial blood was sampled before the induction of anaesthesia during the re-warming phase of CPB (35°C). Blood gas analysis and concentrations of electrolytes, plasma proteins and lactate were measured. The volumes and compositions of fluids administered were recorded.
Results: Factors that were found to correlate significantly (P < 0.05) with the change in hydrogen ion concentration between the two time points were identified. Change in arterial carbon dioxide concentration was used to remove the respiratory component of acidosis. These predictor factors were then entered after change in arterial carbon dioxide tension, to first remove the respiratory component of acidosis, into a multivariate linear regression model (P < 0.001, r 2 = 0.65) so as to examine their influence on the change variance in hydrogen ion concentration. Only the amount of sodium bicarbonate administered (β = -0.404, P < 0.001) and the change in SID (β = -0.339, P = 0.004) were found to predict the change in hydrogen ion concentration. Change in lactate concentration (P = 0.072) and the total volume of fluid administered moderated by body surface area (P = 0.523) were excluded from the model.

Discussion:
Our sample size is underpowered to detect factors that might have a small effect size. Also, the regression model only explained 65% of the variance so factors other than those that we have identified influence the change in hydrogen ion concentration. However, our findings suggest that metabolic acidosis arising during CPB is largely induced by change in the SID and the type of fluids administered, whilst haemodilution and hypoperfusion do not appear to have important roles in its genesis. Whether this metabolic acidosis or its correction has any influence on outcome from cardiac surgery merits further research.
3 An audit of re-admission to intensive care after initial recovery from pulmonary resection: is it worthwhile? Results: ICU and 6-month mortalities were 47% (13 patients) and 64% (18 patients), respectively. Need for mechanical ventilation (P = 0.006) and subsequent renal support (P = 0.05) were predictors of hospital mortality on multivariate analysis. All four patients who required both ventilation and renal support died. Only two of 17 patients (12%) who required mechanical ventilation were alive at 6 months (P = 0.002). Age, sex, preoperative pulmonary function, extent of resection, diagnosis, need for reoperation and inotropic requirements were not predictors of poor outcome. Patients who died in the ICU (n = 13) stayed for longer (mean, 17.6 days versus 5.3 days; P = 0.04) and at a higher average cost per patient (£21,992 versus £5300; P = 0.04) than those who survived (n = 15).

Conclusions:
Mechanical ventilation for subsequent respiratory complications after initial recovery from lung resection is generally not worthwhile. Background: Apoptosis is triggered by a number of intrinsic and extrinsic factors but its importance in ischaemia-reoxygenation in the human heart is unclear. We quantified apoptosis and necrosis in an in vitro model of human atrial myocardium following various periods of simulated ischaemia (SI) and reoxygenation (R).
Methods: Experiments (n = 8 per group) were performed on sections of right atrium subjected to periods of SI (0, 30, 90 and 180 min) followed by R (2, 8 and 24 hours). Cell damage was measured following release of myocyte-specific creatine kinase (CK-MB) and cell viability measured using the vital stain MTT. Cell apoptosis and necrosis were visualised in tissue sections with FITC (TUNEL) and propidium iodide, respectively. Quantification was by confocal microscopy and NIH-image software. Caspase-3like activity was quantified by fluorometric assay.
Results: CK-MB release and necrosis increased whereas MTT values decreased over the period of SI in a dose-dependent manner. Apoptosis increased (32%) after 90 min SI with 2 hours R and peaked (56%) after 90 min SI with 8 hours R. Apoptosis declined following 180 min R. The smallest induction of apoptosis occurred after 24 hours R. With increasing SI in the 2 hour protocol, there was a progressive rise in the ratio of caspase-3 to total caspase activity, which increased to a maximum of fourfold after 180 min SI and 2 hours R. Caspase-3 levels were similar to fresh tissue after 24 hours.

Conclusions:
In this model of SI/R injury of human myocardium, the degree of apoptosis and necrosis varies with the duration of ischaemic insult and the reoxygenation time. After certain periods of ischaemia, apoptosis may be the predominant pathway to cell death. Background: Patients with diabetes mellitus have a worse hospital and long-term outcome after coronary artery bypass grafting (CABG) [1]. It has been shown that the non-insulin diabetes mellitus (NIDDM) group of patients on oral sulphonylureas have a higher mortality than those treated with insulin (IDDM) following myocardial infarction [2]. Oral sulphonylureas abolish ischaemic preconditioning, which is an important cardiac protective mechanism during the perioperative period of CABG [2]. Insulin resistance and hyperglycaemia decrease arterial compliance, promote plaque growth and cause contractile dysfunction of the myocytes [3].

Outcome following coronary artery bypass grafting in patients with non-insulin diabetes mellitus
Objective: To analyse retrospectively outcome data in patients with NIDDM on oral sulphonylureas who underwent CABG.
Methods: From a total of 2537 patients who had CABG, outcome data was identified in 236 patients with NIDDM and in 130 patients with IDDM over a 2-year period (April 1999-March 2001). We compared the mortality, length of hospital stay, length of stay in the intensive care unit (ICU), reoperation rate, ICU re-admission rate and duration of operation with control patients, matched with respect to surgeon and risk score (EuroSCORE). We also compared the incidence of diabetes in Europe and North America with Papworth.
Results: There was no difference in length of hospital stay, length of ICU stay, reoperation rate, ICU re-admission rate and the duration of operation.

Conclusions:
There is a higher mortality in the NIDDM group of patients compared with the IDDM and the non-diabetic group after CABG. Intensive insulin therapy in critically ill postoperative patients showed a reduction in hospital mortality and morbidity from renal failure, blood stream infections and polyneuropathy, and reduced red cell transfusion requirement [4]. Assessment of diabetic patients in the pre-assessment clinics, stopping sulphonylureas and converting to insulin preoperatively and to tight blood glucose control perioperatively, may help improve outcome in this group of patients.  Table 1 Median units of blood product used for the five surviving patients (range)

Product
Before Novo7 After Novo7 Introduction: The non-depolarising muscle relaxant (NDMR) pancuronium continues to be used for fast-track cardiac anaesthesia despite its declining popularity elsewhere. Its duration of action can be unpredictable and prolonged, leading to an increased incidence of residual neuromuscular block [1]. We examined whether pancuronium remains an appropriate NDMR for 'fast-track' patients and include comparison with rocuronium, which has been suggested as an alternative agent.
Methods: Twenty patients eligible for 'fast-track' cardiac surgery were prospectively randomised to receive either pancuronium 0.1 mg/kg or rocuronium 1 mg/kg in a double-blind study design. Neuro-muscular function was assessed by acceleromyography and the time to recovery of train-of-four (TOF) ratio of 0.9 was measured. A standardised anaesthetic technique was employed which avoided the use of volatile anaesthetic gases and vapours.

Results:
Both groups had similar demographic makeup and were well matched for confounding variables. No patient required supplementary doses of NDMR.
No patient in the rocuronium group and 7/10 patients in the pancuronium group had their extubations delayed as a consequence of residual paralysis.

Conclusions:
We have demonstrated that pancuronium lasts approximately twice as long and has approximately double the interindividual variation compared with rocuronium. We recommend that pancuronium is no longer an acceptable NDMR in such patients. Although rocuronium has potential as an alternative agent, we recommend that due to variation in its duration of action posthypothermic cardiopulmonary bypass, patients should routinely have their neuro-muscular function monitored prior to extubation.