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Fulminant pulmonary edema after intramuscular ketamine

From the Department of Anaesthesiology & Critical Care Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences Lucknow and the M.L.N. Medical College Allahabad, India.

Address correspondence to: Dr. Chandra Kant Pandey, Department of Anaesthesiology & Critical Care Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India. Fax: 91-522-440017; E-mail: ckpandey{at}sgpgi.ac.in

	Abstract

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Purpose: To report an unusual case of pulmonary edema following intramuscular ketamine administration.

Clinical Features: An eight-year-old, healthy girl presented for dressing of first degree burns on dorsum of hand. Ten minutes after administration of 125 mg ketamine im, she developed laboured breathing, cyanosis, and bilateral crepitations and arterial blood gas analysis showed PaO₂ 55 mmHg. There was no evidence of upper airway obstruction. On intubating the trachea, pink frothy fluid emerged from the tube. She was diagnosed as a case of neurogenic pulmonary edema. She was managed with positive pressure ventilation with positive end expiratory pressure, morphine and furosemide. With this treatment she showed a favourable recovery.

Conclusion: Ketamine was given im to aid burns dressing in this case because it has distinct advantages above the other anesthetic agents including that of being a good analgesic which is absorbed by im route. Its use led to the development of pulmonary edema.

	Introduction

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PULMONARY edema after heroin, methadone and fentanyl as well as following the abuse of crack cocaine has been reported.^1–5 Also, there is one report of pulmonary edema following ketamine administration in a patient who had a history of crack cocaine abuse.⁶ In animals, pulmonary edema has been described after administration of xylazine-ketamine.⁷ We report a case of pulmonary edema after intramuscular ketamine in a previously healthy girl who presented for burn dressing.

	Case report

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An eight-year-old, 20 kg girl, presented for dressing of first-degree burns approximately 5x5 cm on the dorsum of the left hand. The patient was otherwise healthy, with no underlying medical risk factors. She was not suffering from respiratory disease. On physical examination, heart rate was 98 bpm, BP 100/68 mmHg. On auscultation, the lungs were clear and the cardiovascular system was normal. Noninvasive blood pressure, pulse oximeter and ECG monitoring were applied. The child was lying supine and oxygen 30% was started via a ventimask. Ketamine, 6.25 mg·kg^–1 , was given im to aid the dressing procedure and no other medication was given. Isolyte P at 3 ml·kg^–1·hr^–1 was infused. Ten minutes later, the child developed laboured breathing. Respiration was shallow and at a rate of 30·min^-1. There was no suprasternal or supraclavicular retraction and no "rocking horse" movement of the chest. A patent airway was ensured but she developed cyanosis and oxygen saturation decreased to 80%. Chest auscultation revealed bilateral coarse crepitations. The saturation decreased to 70% very rapidly. The trachea was immediately intubated with 5.0 cuffed endotracheal tube from which emerged a gush of pink frothy fluid. Arterial blood gas analysis showed pH 7.39, PCO₂ 28 mmHg, PO₂ 55 mmHg, HCO₃ 25 mmol·l^–1 and SpO₂ 86% at FiO₂ 0.5. A diagnosis of pulmonary edema was made. She was given 0.1 mg·kg^–1 morphine and 1 mg·kg^–1 frusemide and she was transferred to the intensive care unit where positive pressure ventilation with PEEP of 8 cm H₂O and FiO₂ 1 was instituted. Oxygen saturation increased to 98%. Intermittent endotracheal suction was performed. She was nursed in a propped up position and intermittent suction continued. Chest X-ray one hour after the event was normal. Two hours after positive pressure ventilation at FiO₂ of 0.4, arterial blood gas analysis showed pH 7.44, PCO₂ 38.8, PO₂ 176 mm Hg, HCO₃ 25 mmol·l^–1. Morphine, 0.1 mg·kg^–1 , iv was repeated two hours after the event. She passed 600 ml urine in the next six hours. Isolyte P was infused as a maintenance fluid at 60 ml·hr^–1. She became conscious three hours after the event and the trachea was extubated approximately five hours after arriving in the ICU. She was kept in the intensive care unit over night and was transferred to the surgical ward the next day without complication.

	Discussion

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Ketamine is a hypnotic agent, possessing well-defined analgesic properties and is often used for induction of anesthesia because it has a rapid onset of action, short duration and is less likely to be followed by psychotic symptoms in children. These properties, combined with superb analgesia, give it an advantage in children undergoing repeated neurological investigation, radiotherapy or other minor surgical procedures where it can be given by intramuscular, intravenous, oral or nasal routes.⁸

Pulmonary edema may be caused by either increased pulmonary vascular pressure (cardiogenic), or increased permeability (noncardiogenic).^7,9 Increased pressure pulmonary edema is characterised by lack of cellular damage, and a benign course of development. In contrast, increased permeability pulmonary edema is characterised by presence of cellular damage, protein rich edema fluid and rapid onset. Pulmonary edema following the use of heroin has been attributed to hypoxia, acute allergic reactions, neurogenic effect or a direct toxic effect of heroin on the alveolar capillary membrane.^1,2 Hypoxia produces mild vasoconstriction of pulmonary arteries and arterioles, and increased permeability of alveolar walls.^1,10 This would lead to over-perfusion and raised capillary pressures in uninvolved areas of the lung, which in turn might cause edema of the hydrostatic type. Our patient did have a period of respiratory depression, as was manifested by cyanosis; decreased respiratory depth followed a period of marked hypoventilation and decreased SpO_2. However, since experimental evidence shows that hypoxia causes no such effect, either alone or in conjunction with other forces,¹⁰ the concept of hypoxia induced pulmonary edema is not relevant in this case.

The pulmonary edema associated with airway obstruction, negative pressure pulmonary edema¹¹ is another possible mechanism but is less likely to be the cause because the patient did not develop clinically detectable airway obstruction at any time.

Acute injury to the central nervous system of both man and experimental animals may be followed by the development of acute pulmonary edema.^12–15 This type of edema develops in the absence of pulmonary or cardiac disease and has been reported with many clinical disorders of the central nervous system (CNS). Immediately after injury, there is a massive increase in systemic arterial and venous pressures, and pulmonary arterial, capillary and venous pressures. These changes reflect an extensive transfer of blood from the systemic to the pulmonary circulation, and are similar to the findings after a massive infusion of adrenaline.¹⁰ The injury to the CNS provokes a massive sympathetic discharge, which causes marked increase in pulmonary intravascular pressures, which leads to hydrostatic type edema.^12–15 The increase in the intravascular pressure is short lived, but is of such a degree that it injures the endothelium of small pulmonary blood vessels. This results in increased vascular permeability and small hemorrhages. The increased permeability persists after intravascular pressures have returned to normal, and leads to the escape of edema fluid with a high protein content. This variety of pulmonary edema has been called neurogenic pulmonary edema to distinguish it from other varieties of pulmonary edema and to emphasize the primary role played by the CNS in the pathogenesis.^9,10,13–15 Studies suggest that neurogenic pulmonary edema (NPE) is mediated largely through the sympathetic nervous system, specifically the alpha adrenergic system. The ability to prevent NPE by pre-treatment with adrenergic blocker agents indicates that massive neural discharge is primarily sympathetic in nature. Alpha adrenergic blocking drugs suppress the peripheral effects of sympathetic discharge and thus prevent pulmonary edema. The ability to prevent NPE with a variety of CNS depressants that operate by different pharmacological mechanism suggests that sympathetic discharge is centrally mediated and can be blocked by non-specific central depression.^9,10,12,13 The use of morphine produces dramatic improvement in many cases of acute pulmonary edema.¹⁰ The most probable explanation is that neurogenic induced vasoconstriction, contributes to the rise in intravascular pressure, that precipitates an attack of acute edema, and that morphine abolishes this neurogenic vasoconstriction.

Ketamine is a potent sympathomimetic.⁸ There is at least one report of pulmonary hypertension and pulmonary edema caused by intravenous ketamine in a patient with coronary artery disease.⁶ Even in normal patients, ketamine produces increased pulmonary artery pressure, increased pulmonary vascular resistance and, secondarily, an increase in right ventricular stroke work.⁸ The cardiovascular effects produced by ketamine resemble sympathetic nervous system stimulation. The mechanism for the ketamine induced cardiovascular effects is complex.⁸ Direct stimulation of the central nervous system leading to increased sympathetic nervous system outflow seems to be the most important mechanism.⁸ Another proposed mechanism of the cardiac stimulating effect of ketamine, which has not been confirmed, is inhibition of norepinephrine uptake into postganglionic sympathetic nerve endings resulting in elevated plasma catecholamine concentration.⁸ This seems to be an appropriate explanation for the development of pulmonary edema in the case discussed here.

In view of the widespread casual use of ketamine by surgeons and other clinicians unaware of the possible complications, our case is a precautionary note to avoid misuse of the drug.

Accepted for publication June 14, 2000.

	References

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7 Amouzadeh HR, Sangiah S, Qualls CW Jr, Cowell RL, Mauromoustakos A. Xylazine-induced pulmonary edema in rats. Toxicol Appl Pharmacol 1991; 108: 417–27.[Medline]

8 Stoelting RK. Pharmacology and Physiology in Anesthetic Practice, 2nd ed. Philadelphia: JB Lippincott Co., 1991.

9 Wray NP, Nicotra MB. Pathogenesis of neurogenic pulmonary edema. Am Rev Respir Dis 1978; 118: 783–6.[Medline]

10 Hurley JV. Current views on the mechanisms of pulmonary oedema. J Path 1978; 125: 59–79.

11 Lang SA, Duncan PG, Shephard DAE, Ha HC. Pulmonary oedema associated with airway obstruction. Can J Anaesth 1990; 37: 210–8.[Abstract/Free Full Text]

12 Theodore J, Robin ED. Speculations on neurogenic pulmonary edema (NPE). (Editorial) Am Rev Respir Dis 1976; 113: 405–11.

13 Colice GL, Matthay MA, Bass E, Matthay RA. Neurogenic pulmonary edema. Am Rev Respir Dis 1984; 130: 941–8.[Medline]

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