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Biomedical subjects

K G Hickling

Publications and source records attributed to K G Hickling.

10 recordsLinked to original sources

Serum aminoglycoside clearance is predicted as poorly by renal aminoglycoside clearance as by creatinine clearance in critically ill patients.

OBJECTIVE: To determine the relationships among serum aminoglycoside clearance, renal aminoglycoside clearance, measured creatinine clearance, and estimated creatinine clearance derived from a standard formula in critically ill patients. SETTING: A ten-bed general ICU in a university hospital. PATIENTS: Eighteen critically ill patients who were being treated with gentamicin or tobramycin for severe infections, and were hemodynamically stable. INTERVENTIONS: The various clearances were measured simultaneously after the administration of a dose of aminoglycoside by assaying serial blood samples for aminoglycoside and creatinine concentration, and by measuring the content of these substances in urine collected over the same time period. OUTCOME MEASURES: The slopes, intercepts and coefficients of determination (r2) of the various regressions were determined, along with the 95% confidence intervals for the prediction of serum aminoglycoside clearance from each other variable. RESULTS: Renal aminoglycoside clearance, creatinine clearance, and estimated creatinine clearance accounted for only 58%, 59%, and 62%, respectively, of the variance in serum aminoglycoside clearance. Only 64% of the variance in renal aminoglycoside clearance was explained by creatinine clearance. Substantial and variable nonrenal aminoglycoside clearance was evident. CONCLUSIONS: The 95% confidence intervals for the prediction of serum aminoglycoside clearance from each index of renal function indicated that none of these indices provided acceptable accuracy for the prediction of serum aminoglycoside clearance and dosage requirements in critically ill patients. Renal aminoglycoside clearance was not better than creatinine clearance in this respect, and thus no other index of renal function is likely to be more accurate. This finding implies that the only accurate method of determining the dose requirements to achieve target serum concentrations in such patients will be individualized pharmacokinetic dosing.

Aminoglycosides

Ventilatory management of ARDS: can it affect the outcome?

Animal studies have demonstrated that mechanical ventilation with high peak inspiratory pressure (PIP) results in acute lung injury characterised by hyaline membranes, granulocyte infiltration and increased pulmonary and systemic vascular permeability. This can result in progressive respiratory failure and death. In surfactant deficient lungs this occurs with tidal volumes (Vt) as low as 12 ml/kg, and PIP as low as 25 cm H2O, values which are frequently used clinically. The mechanisms resulting in this form of ventilator induced lung injury are not clear, but it appears to result from global or regional overdistension of the lung or terminal airways. It can be prevented or reduced in severity in some animal models by the use of PEEP. It is suggested that the use of high PIP in some patients may result in progressive deterioration of their ARDS, possibly contributing to mortality both from respiratory failure and other causes. It may be very important to limit PIP by reducing Vt even if this results in hypercapnia and a deterioration of oxygenation in the short term.

Animals

Low mortality associated with low volume pressure limited ventilation with permissive hypercapnia in severe adult respiratory distress syndrome.

Many animal studies have shown that high peak inspiratory pressures (PIP) during mechanical ventilation can induce acute lung injury with hyaline membranes. Since 1984 we have limited PIP in patients with ARDS by reducing tidal volume, allowing spontaneous breathing with SIMV and disregarding hypercapnia. Since 1987 50 patients with severe ARDS with a "lung injury score" greater than or equal to 2.5 and a mean PaO2/FiO2 ratio of 94 were managed in this manner. The mean maximum PaCO2 was 62 mmHg, the highest being 129 mmHg. The hospital mortality was significantly lower than that predicted by Apache II (16% vs. 39.6%, chi 2 = 11.64, p less than 0.001). Only one death was due to respiratory failure, caused by pneumocystis pneumonia. 10 patients had a "ventilator score" greater than 80, which has previously predicted 100% mortality from respiratory failure. Only 2 died, neither from respiratory failure. There was no significant difference in lung injury score, ventilator score, PaO2/FiO2 or maximum PaCO2 between survivors and non-survivors. We suggest that this ventilatory management may substantially reduce mortality in ARDS, particularly from respiratory failure.

Blood Gas Analysis

Assisted ventilation in severe childhood asthma.

Our experience of assisted ventilation in severe childhood asthma over a three year period is reviewed. One per cent of children with an acute attack of asthma required ventilatory support during this time. There were no deaths and no long term sequelae resulting from assisted ventilation. The number of children requiring this type of management however, provides further evidence to support the thesis that asthma is not only common but severe in New Zealand.

Asthma

A retrospective survey of treatment and mortality in aspiration pneumonia.

A retrospective survey was conducted of all patients with severe aspiration pneumonitis requiring artificial ventilation in our Intensive Care Unit from 1982-1986 inclusive. Of 38 patients, 8 (21%) died. Five of these deaths were due to severe primary intracranial pathology, and occurred after complete or almost complete resolution of the pneumonitis. One death (2.5%) due to myocardial infarction was possibly related to aspiration, and 2 deaths (5%) were definitely related to aspiration. The 7.5% mortality related to aspiration is considerably lower than in previous clinical studies of severe aspiration pneumonia. There was only one death due to aspiration in patients under the age of 70. The mean arterial to alveolar oxygen tension ratio was 0.221, and the mean predicted mortality by apache II was 43%. Patients were managed with rapid intravascular volume restoration using crystalloid fluids, early ventilation, no steroids, and no immediate antibiotics. We conclude that with such management it is possible to achieve a low hospital mortality in severe aspiration pneumonia, particularly in young patients.

Adult

Extracorporeal CO2 Removal in severe adult respiratory distress syndrome.

Sixty-five per cent survival has been achieved in a group of patients with severe ARDS and a predicted mortality of 92%, by the use of Gattinoni's technique of extracorporeal CO2 removal. In patients and animals the technique has usually resulted in rapid improvement in the radiographic appearance and lung function. There are several possible mechanisms by which the technique may facilitate lung repair, including improvement of lung tissue oxygenation, the avoidance of high airway pressures and regional alkalosis in the lung, a reduction in oxygen toxicity, and the frequency observed reduction in pulmonary artery pressure. The apparent effectiveness of the technique and other associated evidence have implications which should lead us to reconsider some aspects of our conventional management of patients with severe ARDS.

Alkalosis, Respiratory