Case report
Acta Anaesthesiol Scand 1992: 36: 106-1 07
Use of ketamine in acute severe asthma V. J. SARMA Pitei General Hospital, Pitei, Sweden
Two patients with acute severe asthma, who failed to respond to conventional therapy, were given intravenous ketamine in sub-anaesthetic doses with good results. A bolus dose of 0.75 mg/kg was followed by the same dose over 10 min with relief of bronchospasm in both cases. An infusion of ketamine at a rate of 0.15 mg/ kg/h was used in each case to prevent recurrence of bronchospasm. Intravenous ketamine can be used to relieve acute intractable bronchospasm provided expert anaesthetic help is at hand. A review of the literature concerning its use in such situations is also presented.
Receiued 16 April, accepted 16 3ub 1991
Key words: Bronchospasm; ketamine.
Ketamine was introduced as a dissociative anaesthetic agent by Domino et al. in 1965 (1). Its beneficial effect in the anaesthetic management of asthmatic patients was reported by Corssen et al. (2). Its use in the treatment of severe bronchospasm was first described by Betts & Parkin (3).
CASE REPORTS
'
Case I A 40-year-old woman with a history of severe intrinsic asthma was brought to the Intensive Care Unit after an asthmatic attack. O n admission she was cyanotic, distressed and the breath sounds were barely audible on auscultation. The pulse oximeter read a saturation of 80% and the arterial blood gases showed a Po, of 7.9 kPa and a Pco, of 14.3 and a p H 7.12 on an Fio, of 0.4. She was treated in the Accident and Emergency Unit with intravenous theophyllamine 200 mg, 0.5 mg terbutaline, 200 mg hydrocortisone and 4 mg of racemic adrenaline in a nebulised form. Adrenaline, 0.5 mg, was given intravenously without any effect. Her heart rate was 21 1 beatslmin and her blood pressure was 170/100 mmHg (22.7/13.3 kPa). Positive pressure ventilation using a face mask and etherloxygen mixture was attempted but it was impossible to force air into her lungs. Ketamine, 0.75 mg/kg, was injected as a bolus and the same dose of ketamine was infused slowly in the next 10 min. Her breathing improved and her oxygen saturation was 95%. Ketamine was continued at 0.15 mg/kg/h for 4 h and was then discontinued. Within minutes of discontinuation she became wheezy again and a bolus of 25 mg of ketamine was given and an infusion of 0.15 mg/kg/h was restarted. The bronchospasm resolved with this treatment. After 4 h, ketamine was stopped altogether. During the following 2 days the patient had many mild attacks and these could be managed with theophyllamine and terbutaline infusions. This patient complained of hallucinations and extracorporeal sensations as a result of ketamine infusion. Case 2 A 43-year-old asthmatic female, was brought to the Accident and Emergency Unit with a history of 2 days of fever, cough and dy-
spnoea. She had tried inhalation therapy with terbutaline without any effect. Her blood pressure was 166/105 mmHg (22.2/14.0 kPa) and her heart rate was 160/min. O n auscultation only a few sibilant ronchi could be heard, and breath sounds were diminished bilaterally with scattered crepitations in the left lower lobe. She received 300 mg of theophyllamine intravenously, 8 mg of betamethasone orally, and 0.5 mg terbutaline subcutaneously. As there was no improvement, inhalation of 4 mg of racemic adrenaline was tried, along with 0.5 mg of adrenaline subcutaneously without much improvement. She was transferred to the Intensive Care Unit. O n arrival she was cyanotic and exhausted with an oxygen saturation of 82% on an Fio, of 0.4. Ketamine was injected intravenously as described in the previous case. Her breathing improved within 15 min and the ketamine infusion was reduced to a maintenance dose of 0.15 mg/kg/h. Her blood gases were normal for the next 24 h. Next evening, the doctor in charge felt that she had copious secretions as a result of ketamine and so ordered its discontinuation. Within an hour the patient developed severe bronchospasm and after an unsuccessful trial with intravenous theophyllamine, terbutaline and intravenous adrenaline, she needed to be intubated and ventilated for 5 days with halothanel oxygen and etherloxygen on a circle system.
DISCUSSION Clinical studies with ketamine have shown that it increases pulmonary compliance and decreases airway resistance in patients with obstructive airway disease (2, 4).Most importantly, this bronchodilator effect is evident at subanaesthetic plasma concentrations and hence can be used in spontaneously breathing patients
(5) *
Several workers using isolated animal (6, 7) and human bronchial preparations (8) have shown that ketamine exerted a partial, non-competitive antagonism to histamine and acetylcholine. They found that ketamine had a powerful bronchial relaxant effect and countered the bronchoconstriction caused by a variety of agents.
USE O F KETAMINE IN ACUTE SEVERE ASTHMA
107
The bronchial relaxant effects of ketamine are partly REFERENCES due to the sympathomimetic effects of the drug, as I . Domino EF, Chodoff P, Corssen G. Pharmacologic effects of CI581, a new dissociative anaesthetic in man. Clin. Pharmacol Ther ketamine is known to induce the release of endogenous 1965: 6 279-291. cathecholamines (9), and to inhibit catecholamine re2. Corssen G, Gutierrez J, Reves JG, Huber FC. Ketamine in the uptake processes (10, 1 1 ) . White et al. have found that anesthetic management of asthmatic patients. Anesth Analg 1972: though propranolol blocked the bronchial relaxant ef51: 588-596. 3. Betts GK, Parkin CE. Use of ketamine in an asthmatic child. A fect of epinephrine, it had no effect on ketamine-incase report. Anesth Analg 1971: 50: 420-421. duccd bronchial relaxation, suggesting that ketamine 4. Huber FC, Reves JG, Gutierrez J, Corssen G. Ketamine: its acted on sites other than beta-receptors (12). Ketaeffect on airway resistance in man. Southern Med J 1972: 65: mine is described as having local anaesthetic properties 1 176-1 180. (13) and direct calcium channel blocking effects (14); 5. Park GR, Manara AR, Mendel L, Bateman PE. Ketamine infusion. Its use as a sedative, inotrope and bronchodilator in a at subanaesthetic levels it has the potential to block Ncritically ill patient. Anaesthesia 1987: 42: 980-983. methyl-D-aspartate receptors which mediate the poly6. Wanna HT, Gergis SD. Procaine, lidocaine and ketamine inhibit synaptic excitatory pathways in the mammalian spinal histamine-induced contracture of guinea pig tracheal muscle in cord (15): one or all of these effects probably play a uitro. Anesth Analg 1978: 57: 25-27. 7. Lundy PM, Gowdy CW, Colhoun EH. Tracheal smooth muscle role in the attenuation of bronchospasm in a patient relaxant effect of ketamine. Br 3 Anaesth 1974: 46: 333-336. with intrinsic asthma. 8. Gateau 0, Bourgain JL, Gaudy JH, Benveniste J. Effects of It is suggested that ketamine sensitizes the myocarketamine on isolated human bronchial preparations. Br 3Anaesth dium to endogenous catecholamines and enhances the 1989: 63: 692495. arrhythmogenicity of adrenaline ( 16). However, car9. Zsigmond EK, Kothary SP, Martinez OA, Matsuki A, Kelsch RC. Diazepam for the prevention of the rise in plasma catecholdiac arrhythmias are very uncommon following ketaamines caused by ketamine. Clin Pharmacol Ther 1974: 15: mine and in fact some studies have shown that it has 223-224. an antiarrhythmic action ( 17, 18). In both these cases, 10. Salt PJ, Barnes PK, Beswick FJ. Inhibition of neuronal and despite the presence of intrinsic and extrinsic catecholextraneural uptake of noradrenaline by ketamine in isolated perfused rat heart. BY3 Anaesth 1979: 51: 835-838. amines, ketamine infusion did not result in any cardiac arrhythmias. Hence, it appears to be safer in this situ- 1 I . Cook DJ, Carton EG, Housmans PR. Mechanism of the positive inotropic effect ofketamine in isolated ferret ventricular papillary ation than halothane. muscle. Anesthesiolou 199I: 74: 880-888. Salivary and tracheobronchial mucous gland secre- 12. White PF, Way WL, Trevor AJ. Ketamine - its pharmacology and therapeutic uses. Anesthesiology 1982: 56: 119-136. tions are increased by ketamine (12). However, the use of an antisialogogue in this situation may potentiate 13. Amiot JF, Bouju P, Palacci JH. Intravenous regional anaesthesia with ketamine. Anaesthesia 1985: 40:899-901. the tachycardia caused by adjuvant drugs used in the 14. Abdalla SS, Laravuso RB, Will JA. Ketamine inhibits calcium treatment of bronchospasm. Ketamine is also associinflux in pulmonary arterial smooth muscle. Anesthesiology 1983: ated with emergence delirium type of reactions. A 59: A372. combination of ketamine with benzodiazepines reduces 15. Maurset A, Skoglund LA, Hustveit 0, Oye I. Comparison of ketamine and pethidine in experimental and postoperative pain. the incidence of side-effects. Restall et al. (19) have Pain 1989: 3 8 37-41. used a continuous infusion of midazolam with keta- 16. Hamilton JT, Bryson JS. The effect of ketamine on transmemmine for military surgery and general civilian practice brane potentials of Purkinje fibers of the pig heart. BY 3 Anaesth with good results. Benzodiazepines with their potential 1974: 46: 636-642. for causing respiratory depression must be used with 17. Dowdy EG, Kaya K. Studies of the mechanism ofcardiovascular responses to (3-581. Anesthesiology 1968: 29: 93 1-943. caution in an asthmatic. Though both patients in this 18. Goldberg AH, Keane PW, Phear WPC. Effects of ketamine on report experienced unpleasant psychomimetic reaccontractile performance and excitability of isolated heart muscle. tions during the recovery phase, neither had any recur3 Pharmacol Exp Ther 1970: 175: 388-394. rent experiences. They also expressed a willingness to 19. Restall J, Tully AM, Ward PJ, Kidd AG. Total intravenous anaesthesia for military surgery. A technique using ketamine, have ketamine again in case of an emergency. midazolam and vecuronium. Anaesthesia 1988: 43: 46-49. Ketamine certainly has a place in the treatment of life-threatening bronchospasm but is definitely not advocated as the drug of first choice. Facilities for Address: the control of ventilation and the presence of expert Dr. J? Jayadev Sarma DA, FFARCSI Department of Anaesthetics anaesthetic help are imperative in such situations. Pitei General Hospital 941 28 Pitel Sweden
Acta Anaesthesiol Scand 1992: 36: 106-1 07
Use of ketamine in acute severe asthma V. J. SARMA Pitei General Hospital, Pitei, Sweden
Two patients with acute severe asthma, who failed to respond to conventional therapy, were given intravenous ketamine in sub-anaesthetic doses with good results. A bolus dose of 0.75 mg/kg was followed by the same dose over 10 min with relief of bronchospasm in both cases. An infusion of ketamine at a rate of 0.15 mg/ kg/h was used in each case to prevent recurrence of bronchospasm. Intravenous ketamine can be used to relieve acute intractable bronchospasm provided expert anaesthetic help is at hand. A review of the literature concerning its use in such situations is also presented.
Receiued 16 April, accepted 16 3ub 1991
Key words: Bronchospasm; ketamine.
Ketamine was introduced as a dissociative anaesthetic agent by Domino et al. in 1965 (1). Its beneficial effect in the anaesthetic management of asthmatic patients was reported by Corssen et al. (2). Its use in the treatment of severe bronchospasm was first described by Betts & Parkin (3).
CASE REPORTS
'
Case I A 40-year-old woman with a history of severe intrinsic asthma was brought to the Intensive Care Unit after an asthmatic attack. O n admission she was cyanotic, distressed and the breath sounds were barely audible on auscultation. The pulse oximeter read a saturation of 80% and the arterial blood gases showed a Po, of 7.9 kPa and a Pco, of 14.3 and a p H 7.12 on an Fio, of 0.4. She was treated in the Accident and Emergency Unit with intravenous theophyllamine 200 mg, 0.5 mg terbutaline, 200 mg hydrocortisone and 4 mg of racemic adrenaline in a nebulised form. Adrenaline, 0.5 mg, was given intravenously without any effect. Her heart rate was 21 1 beatslmin and her blood pressure was 170/100 mmHg (22.7/13.3 kPa). Positive pressure ventilation using a face mask and etherloxygen mixture was attempted but it was impossible to force air into her lungs. Ketamine, 0.75 mg/kg, was injected as a bolus and the same dose of ketamine was infused slowly in the next 10 min. Her breathing improved and her oxygen saturation was 95%. Ketamine was continued at 0.15 mg/kg/h for 4 h and was then discontinued. Within minutes of discontinuation she became wheezy again and a bolus of 25 mg of ketamine was given and an infusion of 0.15 mg/kg/h was restarted. The bronchospasm resolved with this treatment. After 4 h, ketamine was stopped altogether. During the following 2 days the patient had many mild attacks and these could be managed with theophyllamine and terbutaline infusions. This patient complained of hallucinations and extracorporeal sensations as a result of ketamine infusion. Case 2 A 43-year-old asthmatic female, was brought to the Accident and Emergency Unit with a history of 2 days of fever, cough and dy-
spnoea. She had tried inhalation therapy with terbutaline without any effect. Her blood pressure was 166/105 mmHg (22.2/14.0 kPa) and her heart rate was 160/min. O n auscultation only a few sibilant ronchi could be heard, and breath sounds were diminished bilaterally with scattered crepitations in the left lower lobe. She received 300 mg of theophyllamine intravenously, 8 mg of betamethasone orally, and 0.5 mg terbutaline subcutaneously. As there was no improvement, inhalation of 4 mg of racemic adrenaline was tried, along with 0.5 mg of adrenaline subcutaneously without much improvement. She was transferred to the Intensive Care Unit. O n arrival she was cyanotic and exhausted with an oxygen saturation of 82% on an Fio, of 0.4. Ketamine was injected intravenously as described in the previous case. Her breathing improved within 15 min and the ketamine infusion was reduced to a maintenance dose of 0.15 mg/kg/h. Her blood gases were normal for the next 24 h. Next evening, the doctor in charge felt that she had copious secretions as a result of ketamine and so ordered its discontinuation. Within an hour the patient developed severe bronchospasm and after an unsuccessful trial with intravenous theophyllamine, terbutaline and intravenous adrenaline, she needed to be intubated and ventilated for 5 days with halothanel oxygen and etherloxygen on a circle system.
DISCUSSION Clinical studies with ketamine have shown that it increases pulmonary compliance and decreases airway resistance in patients with obstructive airway disease (2, 4).Most importantly, this bronchodilator effect is evident at subanaesthetic plasma concentrations and hence can be used in spontaneously breathing patients
(5) *
Several workers using isolated animal (6, 7) and human bronchial preparations (8) have shown that ketamine exerted a partial, non-competitive antagonism to histamine and acetylcholine. They found that ketamine had a powerful bronchial relaxant effect and countered the bronchoconstriction caused by a variety of agents.
USE O F KETAMINE IN ACUTE SEVERE ASTHMA
107
The bronchial relaxant effects of ketamine are partly REFERENCES due to the sympathomimetic effects of the drug, as I . Domino EF, Chodoff P, Corssen G. Pharmacologic effects of CI581, a new dissociative anaesthetic in man. Clin. Pharmacol Ther ketamine is known to induce the release of endogenous 1965: 6 279-291. cathecholamines (9), and to inhibit catecholamine re2. Corssen G, Gutierrez J, Reves JG, Huber FC. Ketamine in the uptake processes (10, 1 1 ) . White et al. have found that anesthetic management of asthmatic patients. Anesth Analg 1972: though propranolol blocked the bronchial relaxant ef51: 588-596. 3. Betts GK, Parkin CE. Use of ketamine in an asthmatic child. A fect of epinephrine, it had no effect on ketamine-incase report. Anesth Analg 1971: 50: 420-421. duccd bronchial relaxation, suggesting that ketamine 4. Huber FC, Reves JG, Gutierrez J, Corssen G. Ketamine: its acted on sites other than beta-receptors (12). Ketaeffect on airway resistance in man. Southern Med J 1972: 65: mine is described as having local anaesthetic properties 1 176-1 180. (13) and direct calcium channel blocking effects (14); 5. Park GR, Manara AR, Mendel L, Bateman PE. Ketamine infusion. Its use as a sedative, inotrope and bronchodilator in a at subanaesthetic levels it has the potential to block Ncritically ill patient. Anaesthesia 1987: 42: 980-983. methyl-D-aspartate receptors which mediate the poly6. Wanna HT, Gergis SD. Procaine, lidocaine and ketamine inhibit synaptic excitatory pathways in the mammalian spinal histamine-induced contracture of guinea pig tracheal muscle in cord (15): one or all of these effects probably play a uitro. Anesth Analg 1978: 57: 25-27. 7. Lundy PM, Gowdy CW, Colhoun EH. Tracheal smooth muscle role in the attenuation of bronchospasm in a patient relaxant effect of ketamine. Br 3 Anaesth 1974: 46: 333-336. with intrinsic asthma. 8. Gateau 0, Bourgain JL, Gaudy JH, Benveniste J. Effects of It is suggested that ketamine sensitizes the myocarketamine on isolated human bronchial preparations. Br 3Anaesth dium to endogenous catecholamines and enhances the 1989: 63: 692495. arrhythmogenicity of adrenaline ( 16). However, car9. Zsigmond EK, Kothary SP, Martinez OA, Matsuki A, Kelsch RC. Diazepam for the prevention of the rise in plasma catecholdiac arrhythmias are very uncommon following ketaamines caused by ketamine. Clin Pharmacol Ther 1974: 15: mine and in fact some studies have shown that it has 223-224. an antiarrhythmic action ( 17, 18). In both these cases, 10. Salt PJ, Barnes PK, Beswick FJ. Inhibition of neuronal and despite the presence of intrinsic and extrinsic catecholextraneural uptake of noradrenaline by ketamine in isolated perfused rat heart. BY3 Anaesth 1979: 51: 835-838. amines, ketamine infusion did not result in any cardiac arrhythmias. Hence, it appears to be safer in this situ- 1 I . Cook DJ, Carton EG, Housmans PR. Mechanism of the positive inotropic effect ofketamine in isolated ferret ventricular papillary ation than halothane. muscle. Anesthesiolou 199I: 74: 880-888. Salivary and tracheobronchial mucous gland secre- 12. White PF, Way WL, Trevor AJ. Ketamine - its pharmacology and therapeutic uses. Anesthesiology 1982: 56: 119-136. tions are increased by ketamine (12). However, the use of an antisialogogue in this situation may potentiate 13. Amiot JF, Bouju P, Palacci JH. Intravenous regional anaesthesia with ketamine. Anaesthesia 1985: 40:899-901. the tachycardia caused by adjuvant drugs used in the 14. Abdalla SS, Laravuso RB, Will JA. Ketamine inhibits calcium treatment of bronchospasm. Ketamine is also associinflux in pulmonary arterial smooth muscle. Anesthesiology 1983: ated with emergence delirium type of reactions. A 59: A372. combination of ketamine with benzodiazepines reduces 15. Maurset A, Skoglund LA, Hustveit 0, Oye I. Comparison of ketamine and pethidine in experimental and postoperative pain. the incidence of side-effects. Restall et al. (19) have Pain 1989: 3 8 37-41. used a continuous infusion of midazolam with keta- 16. Hamilton JT, Bryson JS. The effect of ketamine on transmemmine for military surgery and general civilian practice brane potentials of Purkinje fibers of the pig heart. BY 3 Anaesth with good results. Benzodiazepines with their potential 1974: 46: 636-642. for causing respiratory depression must be used with 17. Dowdy EG, Kaya K. Studies of the mechanism ofcardiovascular responses to (3-581. Anesthesiology 1968: 29: 93 1-943. caution in an asthmatic. Though both patients in this 18. Goldberg AH, Keane PW, Phear WPC. Effects of ketamine on report experienced unpleasant psychomimetic reaccontractile performance and excitability of isolated heart muscle. tions during the recovery phase, neither had any recur3 Pharmacol Exp Ther 1970: 175: 388-394. rent experiences. They also expressed a willingness to 19. Restall J, Tully AM, Ward PJ, Kidd AG. Total intravenous anaesthesia for military surgery. A technique using ketamine, have ketamine again in case of an emergency. midazolam and vecuronium. Anaesthesia 1988: 43: 46-49. Ketamine certainly has a place in the treatment of life-threatening bronchospasm but is definitely not advocated as the drug of first choice. Facilities for Address: the control of ventilation and the presence of expert Dr. J? Jayadev Sarma DA, FFARCSI Department of Anaesthetics anaesthetic help are imperative in such situations. Pitei General Hospital 941 28 Pitel Sweden
