ANESTHESIA AND ANALGESIA , . , Current Researches VOL.56, NO.4, JULY-AUGUST, 1977
587
Tobramycin-Curare Interaction PETER M. WATERMAN, M D *
R.
BRIAN SMITH, M D t
Pittsburgh, Pennslyvania $
A 59-year-old patient had urologic surgery under d-tubocurarine-fentanyl-NzOanesthesia. The muscle relaxant was reversed with prostigmine at the end of the 5-hour procedure.
Reparalysis occurred after the administration of IV tobramycin and was successfully reversed with prostigmine.
M
Physical examination was unremarkable. X-ray of the right femur showed a lytic lesion. An IVP demonstrated left hydronephrosis with obstruction a t the left ureter and a bladder mass consistent with tumor. Liver and spleen scans were normal as were routine liver-function tests.
than 120 reports concerning augmentation by antibiotics of neuromuscular blockade from muscle relaxants have appeared in the literature.’-5 These blocks have been inconsistently reversed by such agents as calcium, neostigmine, sodium bicarbonate, caffeine sodium benzoate, and carbon dioxide. Factors such as respiratory acidosis, hypothermia, increased magnesium ion, and decreased calcium may also augment the effects of the neuromuscular blocking agents.”-” ORE
This is a case report of reparalysis following the administration of tobramycin in a patient who previously had received d-tubocurarine (dTc) . Although it has been shown*O that cats given extremely high doses of tobramycin (40 mg/kg) developed neuromuscular blockade and respiratory paralysis, this has not been previously reported in man.
CASE REPORT A 59-year-old, 78-kg man presented with hematuria. His past medical history included transitional cell bladder tumor and adenocarcinoma of the prostate. He had undergone numerous cystoscopies and transurethral resections without incident.
The electrocardiogram and chest x-ray, CBC, urinalysis, and serum electrolytes were normal. The patient was scheduled to undergo cystoscopy, bladder biopsy, and retrograde pyelogram. Orthopedic consultation was obtained to evaluate the patient’s right femoral lytic lesion. It was decided to insert a rod prophylactically into the patient’s femur a t the time of his urologic operation. The evening prior to operation, the patient was started on tobramycin ( 8 0 mg, and cefazolin (1 gm) I M every 6 hours. Premedication consisted of morphine ( 10 mg) , hydroxyzine ( 100 mg) , and glycopyrrolate (0.2 mg) IM, 30 minutes before operation. Induction of anesthesia was with thiamylal (300 mg). Tracheal intubation was facilitated by succinylcholine ( 100 nig) , after 3 mg dTc, and the larynx was sprayed with 3 ml of 4 percent lidocaine. Anesthetic
*Assistant Professor, Department of Anesthesiology. .!Professor and Vice Chairman, Department of Anesthesiology. $Department of Anesthesiology, University Health Center of Pittsburgh, Pittsburgh, Pennsylvania 15261. Paper received: 7/9/76 Accepted for publication: 11/29/76
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ANESTHESIAA N D ANALGESIA . . . Current Researches VOL. 56, No. 4, JULY-AUGUST,1977
maintenance consisted of dTc and fentanyl supplementation of N,O. Monitoring was with an esophageal stethoscope, blood-pressure cuff, cardioscope, and peripheral nerve stimulator. Total doses of dTc and fentanyl over 5 hours were 72 mg and 0.85 mg. respectively. Urine output was 950 ml. Atropine ( 1.5 mg) and prostigmine 13 mg) were used to reverse the muscle relaxant. The patient was extubated in the operating room prior to transport to the recovery room. The peripheral nerve stimulator a t that time showed a vigorous twitch response without fade of tetanus and post-tetanic potentiation itetanic frequency-50 Hz) .
measurable blood levels for 8 hours. Infusions administered over a 1-hour period yield similar concontrations.
Fifteen minutes later, 80 mg of tobramycin was added to a Pediatrol” and slowly infused. Forty-five minutes later, before all of the tobramycin was infused, the patient began to complain of difficulty breathing and appeared dyspneic. Muscle strength, which had previously been excellent, was now markedly diminished. The peripheral nerve stimulator showed evidence of nondepolarizing neuromuscular blockade, with diminished twitch, fade of tetanus, and marked post-tetanic potentiation. Tobramycin was discontinued and prostigmine 12.5 mg) and atropine (1.25 mg) were administered IV. Increased grip strength and relief of respiratory difficulty resulted within 3 minutes. After the 2nd reversal, arterial blood gases while the patient wa5 breathing 100 percent O1 via a facemask were pH 7.38, Pam, 38, Pao, 72, HCO1 22, BE/D -2.
In this patient, the time course and sequence of events suggests that the tobramycin augmented the effects of residual dTc and was successfully reversed by prostigmine. The neuromuscular blocking capability of the aminoglycosides has been shown in experimental animalsl.:’ ‘; 7 , l “ but we believe this to be the first reported case of neuromuscular blockade augmentation by this antibiotic and its associated reversal by prostigmine in man.
Twenty minutes later, the remainder of the tobramycin infusion was restarted slowly without incident. Since the infusion in the recovery room had already been over a 45-minute period, the remaining dose of tobramycin was felt to be too small to be of neuromuscular significance. The next full dose of tobramycin was not given until 24 hours later. Repeated arterial blood gases were normal, and he made an uneventful recovery. DISCUSSION Tobramycin sulfate is a water-soluble antibiotic of the aminoglycoside group, that inhibits the synthesis of protein in bacterial cells.”’ I t is reportedly active against most strains of Pseudomonas aeruginosa, Proteus, E coli, Citrobacter, Prouidencia, Staphylococci, and group D Streptococci. Intramuscular injections of 1 mg/kg result in maximum serum concentrations of 4 pg/ml with
Tobramycin is eliminated almost exclusively by glomerular filtration, with renal clearance similar to that of creatinine. Virtually no protein binding occurs in the serum. In patients with normal renal function, up to 84 percent of the dose is recoverable from the urine in 8 hours and up to 93 percent by 24 hours. In the face of normal renal function, the serum half-life is 2 hours. An inverse relationship exists between serum half-life and creatinine clearance.
REFERENCES 1. I’iltinger CR, Eryasa Y, Adamson It: Antibiotic-induced paralysis. Anesth Analg 49: 487-501, 1970 2. Van Nyhuis IS, Miller 1 3 3 , Fogdall RP: The interaction between d-tubocurarine, panruroniuni, polymyxin B and neostigmine on neuromuscular function. Anesth Analg 55: 224-228, 1976 3. Samuelson RJ, Giesecke AH J r , Kallus FT, Stanley x.7F: Lincomycin-curare interaction. Anesth Analg 54: 103-105, 1975 4. Fogdall RP, Miller RD: Prolongation of a pancuronium-induced neuromuscular blockade by Clindamycin. Anesthesiology 41: 407-408, 1974
5. Fogdall RP, Miller RD: Prolongation of a pancuronium-induced neuromuscular blockade by polymixin B. Anesthesiology 40:x4-87, 1974
6. Miller RD: Antagonism of neuromuscular blockade. Anesthesiology 44: 318-329, 1976
5. Foldes F F : Factors which alter the effects of muscle relaxants. Anesthesiology 20: 464504, 1959 8. Miller RD, Van Nyhuis 1 3 , Eger EI 11: T h e effec,t o f temperature on a d-tubocurarine neuromusclrlar blockade and its antagonism by neostigmine. ,J Pharmacol Exp Ther 195:237-242, 1975 9. I3’eldman SA: Effect of changes in electrolytes, hydration and pH upon the reactions to muscle relaxants. Hr J Anaesth 35:546-551, 1963
10. Manufacturer’s Drug Information: NebcinBEli I d l y and Company, Indianapolis, Indiana.
587
Tobramycin-Curare Interaction PETER M. WATERMAN, M D *
R.
BRIAN SMITH, M D t
Pittsburgh, Pennslyvania $
A 59-year-old patient had urologic surgery under d-tubocurarine-fentanyl-NzOanesthesia. The muscle relaxant was reversed with prostigmine at the end of the 5-hour procedure.
Reparalysis occurred after the administration of IV tobramycin and was successfully reversed with prostigmine.
M
Physical examination was unremarkable. X-ray of the right femur showed a lytic lesion. An IVP demonstrated left hydronephrosis with obstruction a t the left ureter and a bladder mass consistent with tumor. Liver and spleen scans were normal as were routine liver-function tests.
than 120 reports concerning augmentation by antibiotics of neuromuscular blockade from muscle relaxants have appeared in the literature.’-5 These blocks have been inconsistently reversed by such agents as calcium, neostigmine, sodium bicarbonate, caffeine sodium benzoate, and carbon dioxide. Factors such as respiratory acidosis, hypothermia, increased magnesium ion, and decreased calcium may also augment the effects of the neuromuscular blocking agents.”-” ORE
This is a case report of reparalysis following the administration of tobramycin in a patient who previously had received d-tubocurarine (dTc) . Although it has been shown*O that cats given extremely high doses of tobramycin (40 mg/kg) developed neuromuscular blockade and respiratory paralysis, this has not been previously reported in man.
CASE REPORT A 59-year-old, 78-kg man presented with hematuria. His past medical history included transitional cell bladder tumor and adenocarcinoma of the prostate. He had undergone numerous cystoscopies and transurethral resections without incident.
The electrocardiogram and chest x-ray, CBC, urinalysis, and serum electrolytes were normal. The patient was scheduled to undergo cystoscopy, bladder biopsy, and retrograde pyelogram. Orthopedic consultation was obtained to evaluate the patient’s right femoral lytic lesion. It was decided to insert a rod prophylactically into the patient’s femur a t the time of his urologic operation. The evening prior to operation, the patient was started on tobramycin ( 8 0 mg, and cefazolin (1 gm) I M every 6 hours. Premedication consisted of morphine ( 10 mg) , hydroxyzine ( 100 mg) , and glycopyrrolate (0.2 mg) IM, 30 minutes before operation. Induction of anesthesia was with thiamylal (300 mg). Tracheal intubation was facilitated by succinylcholine ( 100 nig) , after 3 mg dTc, and the larynx was sprayed with 3 ml of 4 percent lidocaine. Anesthetic
*Assistant Professor, Department of Anesthesiology. .!Professor and Vice Chairman, Department of Anesthesiology. $Department of Anesthesiology, University Health Center of Pittsburgh, Pittsburgh, Pennsylvania 15261. Paper received: 7/9/76 Accepted for publication: 11/29/76
588
ANESTHESIAA N D ANALGESIA . . . Current Researches VOL. 56, No. 4, JULY-AUGUST,1977
maintenance consisted of dTc and fentanyl supplementation of N,O. Monitoring was with an esophageal stethoscope, blood-pressure cuff, cardioscope, and peripheral nerve stimulator. Total doses of dTc and fentanyl over 5 hours were 72 mg and 0.85 mg. respectively. Urine output was 950 ml. Atropine ( 1.5 mg) and prostigmine 13 mg) were used to reverse the muscle relaxant. The patient was extubated in the operating room prior to transport to the recovery room. The peripheral nerve stimulator a t that time showed a vigorous twitch response without fade of tetanus and post-tetanic potentiation itetanic frequency-50 Hz) .
measurable blood levels for 8 hours. Infusions administered over a 1-hour period yield similar concontrations.
Fifteen minutes later, 80 mg of tobramycin was added to a Pediatrol” and slowly infused. Forty-five minutes later, before all of the tobramycin was infused, the patient began to complain of difficulty breathing and appeared dyspneic. Muscle strength, which had previously been excellent, was now markedly diminished. The peripheral nerve stimulator showed evidence of nondepolarizing neuromuscular blockade, with diminished twitch, fade of tetanus, and marked post-tetanic potentiation. Tobramycin was discontinued and prostigmine 12.5 mg) and atropine (1.25 mg) were administered IV. Increased grip strength and relief of respiratory difficulty resulted within 3 minutes. After the 2nd reversal, arterial blood gases while the patient wa5 breathing 100 percent O1 via a facemask were pH 7.38, Pam, 38, Pao, 72, HCO1 22, BE/D -2.
In this patient, the time course and sequence of events suggests that the tobramycin augmented the effects of residual dTc and was successfully reversed by prostigmine. The neuromuscular blocking capability of the aminoglycosides has been shown in experimental animalsl.:’ ‘; 7 , l “ but we believe this to be the first reported case of neuromuscular blockade augmentation by this antibiotic and its associated reversal by prostigmine in man.
Twenty minutes later, the remainder of the tobramycin infusion was restarted slowly without incident. Since the infusion in the recovery room had already been over a 45-minute period, the remaining dose of tobramycin was felt to be too small to be of neuromuscular significance. The next full dose of tobramycin was not given until 24 hours later. Repeated arterial blood gases were normal, and he made an uneventful recovery. DISCUSSION Tobramycin sulfate is a water-soluble antibiotic of the aminoglycoside group, that inhibits the synthesis of protein in bacterial cells.”’ I t is reportedly active against most strains of Pseudomonas aeruginosa, Proteus, E coli, Citrobacter, Prouidencia, Staphylococci, and group D Streptococci. Intramuscular injections of 1 mg/kg result in maximum serum concentrations of 4 pg/ml with
Tobramycin is eliminated almost exclusively by glomerular filtration, with renal clearance similar to that of creatinine. Virtually no protein binding occurs in the serum. In patients with normal renal function, up to 84 percent of the dose is recoverable from the urine in 8 hours and up to 93 percent by 24 hours. In the face of normal renal function, the serum half-life is 2 hours. An inverse relationship exists between serum half-life and creatinine clearance.
REFERENCES 1. I’iltinger CR, Eryasa Y, Adamson It: Antibiotic-induced paralysis. Anesth Analg 49: 487-501, 1970 2. Van Nyhuis IS, Miller 1 3 3 , Fogdall RP: The interaction between d-tubocurarine, panruroniuni, polymyxin B and neostigmine on neuromuscular function. Anesth Analg 55: 224-228, 1976 3. Samuelson RJ, Giesecke AH J r , Kallus FT, Stanley x.7F: Lincomycin-curare interaction. Anesth Analg 54: 103-105, 1975 4. Fogdall RP, Miller RD: Prolongation of a pancuronium-induced neuromuscular blockade by Clindamycin. Anesthesiology 41: 407-408, 1974
5. Fogdall RP, Miller RD: Prolongation of a pancuronium-induced neuromuscular blockade by polymixin B. Anesthesiology 40:x4-87, 1974
6. Miller RD: Antagonism of neuromuscular blockade. Anesthesiology 44: 318-329, 1976
5. Foldes F F : Factors which alter the effects of muscle relaxants. Anesthesiology 20: 464504, 1959 8. Miller RD, Van Nyhuis 1 3 , Eger EI 11: T h e effec,t o f temperature on a d-tubocurarine neuromusclrlar blockade and its antagonism by neostigmine. ,J Pharmacol Exp Ther 195:237-242, 1975 9. I3’eldman SA: Effect of changes in electrolytes, hydration and pH upon the reactions to muscle relaxants. Hr J Anaesth 35:546-551, 1963
10. Manufacturer’s Drug Information: NebcinBEli I d l y and Company, Indianapolis, Indiana.
