Critical Volume for pulmonary acid aspiration: reappraisal in a primate model

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3 dicembre 2016
  1. D. M. RAIDOO, B.SC., M.B., CH.B.,
  2. D. A. ROCKE, M.R.C.P.(U.K.), F.F.A.(S.A.),
  3. J. G. BROCK-UTNE, M.A., M.B., B.CH.(T.C.D.), F.F.A. (S.A.), M.D.(BERGEN),
  4. A. MARSZALEK, M.B., B.S.(POLAND) and
  5. H. E. ENGELBRECHT, M.B., CH.B., D.M.R.D., R.C.P.R.C.S., F.F.R., M.R.C.P.

Abstract

We have studied, in the monkey, the critical volume for the production of severe pneumonitis following pulmonary aspiration of gastric contents. Aspiration of 0.4 ml kg−1 and 0.6 ml kg−1 at pH 1 produced mild to moderate clinical and radiological changes, but no deaths. Aspiration of 0.8 ml kg−1 and 1.0 ml kg−1 at pH 1 was associated with an increasingly severe pneumonitis. At 1.0 ml kg−1, 50% of the animals died—a mortality rate considerably less than that reported previously in animal studies. If these results were to be extrapolated to humans, the critical volume for severe aspiration could be increased from 25 ml to 50 ml (0.8 ml kg−1), considerably reducing the percentage of patients perceived to be “at risk”.

 

Methods and Results

The study was conducted following approval by the University of Natal Ethics and Professional Standards Committee. Twenty-four juvenile monkeys (Cercopithecus aethiops) (mean (SD) weight 2.82 (0.86) kg) were allocated randomly to four groups according to the volume of gastric aspirate administered. Animals were anaesthetized initially with ketamine 30 mg i.v., following which an orogastric tube was inserted and gastric contents aspirated. Aspirate was obtained from several animals on the morning of each study day and was pooled, and homogenized manually. The pH of the aspirate was measured and adjusted to pH 1 by addition of hydrochloric acid: whilst the aspirate was stirred continually using a magnetic stirrer, three to six drops of hydrochloric acid (HC1) 1 mol litre”1 (pH 0.5) were added until the pH of the aspirate was approximately 1. Thereafter, one to six drops of HC1 0.1 mol litre”1 (pH 1.10) were added to bring the aspirate to precisely pH 1. Monkeys were weighed and examined clinically for signs of infection or cardiorespiratory disease. Any animal with a heart rate > 140 beat min”1 or a ventilatory frequency > 40 b.p.m. was excluded from the study. Following this examination, the trachea was intubated and the position of the tube verified both clinically and by chest radiography, the latter being used also to exclude pulmonary disease. Animals were allocated randomly to receive gastric aspirate of differing volumes: group I 0.4 ml kg”1 ; group II 0.6 ml kg”1 ; group III 0.8 ml kg”1 ; group IV 1.0 ml kg”1 . Aspirate was drawn up into a syringe using a 21-gauge needle which was instilled, by the same investigator (D.M.R.), into the lumen of the tracheal tube. Animals were allowed to breathe spontaneously during pulmonary instillation of gastric aspirate. Immediately upon completion of injection of aspirate, the lungs were ventilated for a period of 1 min with a tidal volume of 20 ml kg”1 using a Starling pump, to ensure widespread distribution of die aspirate. Following ventilation, the tracheal tube was removed and animals transferred to an observation room for 6 h. During the observation period, anaesthesia was maintained with diazepam supplemented with ketamine given i.v. via a glucose-saline infusion of 5 drops kg”1 min”1 (paediatric giving set—60 drops ml”1 ). During the period after aspiration, temperature, heart rate, ventilatory frequency, degree of cyanosis (mild, moderate, severe) and presence or absence of wheezing on auscultation were noted. Observers were unaware of the volume of aspiration. Observations were made at 5-min intervals for 30 min, at 15-min intervals for the next 90 min and every 30 min for the remaining 4 h. Chest radiography was repeated at 2 and 6 h after aspiration. Six hours after aspiration, monkeys were allowed to recover, and were housed in separate cages for the next 24 h. Food and water was provided ad libitum and animals observed for signs of respiratory distress. Euthanasia was permitted if severe distress occurred, but this was not required for any animal. Chest radiography and clinical examination were repeated daily under ketamine anaesthesia until recovery. Any animal that died during the study period underwent immediate postmortem (A.M.) during which the lungs and trachea were removed for subsequent histological examination. Lungs were fixed in formalin, and subsequent paraffin-embedded histological sections, stained with haematoxylin and eosin, were examined under light microscopy. Before the definitive study, two additional monkeys were subjected to aspiration of dionosil 1 ml kg”1 , pH 3.8 to demonstrate the efficacy of the methodology. None of the animals died in either the 0.4- or 0.6-ml kg”1 groups. One animal died in the 0.8-ml kg”1 group 12 h after aspiration, and three animals died in the 1-ml kg”1 group. In this last group, two animals died within 2 h of aspiration