Comparison of Propofol Versus Ketarnine for Anesthesia in Pediatric Patients Undergoing Cardiac Catheterization Saul Lebovic, MD, David L. Reich, George Silvay, MD, PhD
MD,
L. Gary Steinberg,
MD,
Frances P. Vela, RN, and
Departments of Anesthesiology and Pediatrics, The Mount Sinai Medical Center, New York, New York
Intravenous propofol was compared with ketamine in 20 pediatric patients undergoing cardiac catheterization. The study patients were randomly assigned to treatment groups so that 10 patients received ketamine and 10 patients received propofol. The hernodynamic responses and recovery characteristics of the two groups were compared. On induction of anesthesia, seven patients in the propofol group experienced a transient decrease in mean arterial blood pressure greater than 20% of baseline accompanied by mild arterial desaturation in four patients. Only one patient in the ketamine group experienced such a decrease in arterial blood pressure. This was the only significant difference ( P < 0.05) in hemodv-
T
he goals for anesthetic management of pediatric patients scheduled to undergo cardiac catheterization include immobility, sedation, and cardiovascular stability. The maintenance of spontaneous ventilation without supplemental oxygen is also desirable so that the normal physiology is least altered by the anesthetic technique. Intravenous ketamine is an agent with a long history of successful use in the cardiac catheterization suite but is associated with hemodynamic aiterations, dysphoric emergence reactions, and a prolonged recovery period (1). Propofol is a substituted phenol anesthetic that is associated with smooth induction of, and rapid recovery from, anesthesia (2). Its pharmacokinetic profile favors administration by continuous intravenous infusion to provide complete anesthesia ( 3 ) .Its safety and efficacy in pediatric patients have been demonstrated in numerous studies (4-6). Reported side effects include pain on injection into small veins (which may be prevented by pretreatment with small doses of intravenous lidocaine) (7) and dose-related decreases in blood pressure and cardiac output. ~
Accepted for publication November 25, 1991. Address correspondence to Dr. Reich, Department of Anesthesiology, Box 1010, The Mount Sinai Medical Center, One Gustave L. Levy Place, New York, NY 10029-6574.
490
Anesth Analg 1992;74:4904
namic effects between the two groups. Time to full recoverv (mean t SD) was significantly less in the propofol group (24 2 19 min vs 139 * 87 min, P < 0.001). In the ketamine group only, significant correlations (I)< 0.05) included time to full recovery with duration of anesthetic ( r = 0.71) and time to full recovery with total drug dose per kilogram (r = 0.82). The authors conclude that propofol anesthesia is a practical alternative for pediatric patients undergoing elective cardiac catheterization and may be preferable to ketamine because of the significantly shorter recoverv time. (Anesth Analg 1992;74:4904)
The current study compared propofol with ketamine for intravenous anesthesia in pediatric patients undergoing cardiac catheterization. This is the first report describing the use of propofol in pediatric patients with congenital heart disease.
Methods After approval of the protocol had been received from the Institutional Review Board, written informed consent was obtained from the parent or guardian. Twenty patients, aged 7 mo to 6 yr, ASA physical status I1 and 111, scheduled for elective cardiac catheterization for evaluation of congenital heart disease were studied. Patients requiring mechanical ventilation or intravenous inotropic support were excluded from the study. No patient received preanesthetic medication, and after a 6-h fast, they arrived in the catheterization laboratory with a n intravenous catheter in situ. The patients were randomly assigned to one of two treatment groups to receive either propofol or ketamine as their anesthetic. Monitoring included a chest stethoscope, electrocardiographic lead 11, a Dinamap blood pressure device, and Nellcor digital pulse oximetry. Heart rate (HR), arterial blood pressure, and preductal digital oxygen saturation (Sp0.J G1992 by
the International Anesthesia Research Society 0003-2999192/$5 00
ANESTH ANALG 1992;74:490-4
were recorded every 5 min for the duration of the study. On arrival in the cardiac catheterization laboratory and after the measurement of baseline Spo, and arterial blood pressure, all patients received glycopyrrolate, 3 pg/kg IV. Patients in the propof01 group received an analgesic dose of fentanyl, 1 pglkg, followed by propofol in 0.5-mgikg boluses every 60 s titrated to an appropriate level of sedation (immobility, tolerance of limb restraints and of preparation of the groin with antiseptic solution). An hourly infusion rate of three times the total induction dose of propofol was administered for maintenance of anesthesia. To decrease the likelihood of pain on injection, the propofol emulsion was diluted 1:l with 5% dextrose solution, and the induction dose was preceded by intravenous lidocaine (0.1 mL/kg of a 0.1% solution). Patients in the ketamine group received ketamine, 2 mgikg, as an intravenous bolus, followed by an infusion of 2 mg.kg-'.h-'. In addition, midazolam, 0.02 mgikg, was administered hourly to prevent emergence delirium. The investigators were not blinded to the experimental groups during the procedure. If patient movement or crying occurred in either group, a bolus of one-half the total induction dose was administered and the infusion rate was increased by 50%. Changes in mean arterial blood pressure (MAP) or HR >20% from awake baseline values were noted. Decreases in digital pulse oximetry (SpoJ >5 points from the awake baseline value were noted. The results of arterial blood gas analyses were recorded whenever they were performed. Anesthetic drug infusions were discontinued when the groin bandage had been applied and the duration of the anesthetic and total drug doses were recorded. Postanesthesia recovery scores, modified from the method of Steward (8), were determined by an independent blinded observer from the time the infusion was stopped until discharge from the recovery room (Table 1). Results are expressed as the mean 2 SD. Data were analyzed using the unpaired Student's t-test, Fisher's exact test, and Pearson's linear regression analysis. Correlation coefficients were compared using Z-transformations. A P value < 0.05 was considered significant.
Results All patients completed the study protocol and no patient required supplemental oxygen. There were no statistically significant differences between the groups with respect to age, weight, duration of catheterization, and baseline Spo, on room air. Demographic data are summarized in Table 2.
PEDIATRIC ANESTHESIA LEBOVIC ET AL. CARDIAC CATHETERIZATION ANESTHESIA
491
Table 1. Recovery Scoring System" Consciousness Awake Responds to verbal stimuli Responds to tactile stimuli Not responding Airway Cough on command or cry Maintains good airway Requires airway assistance
2 1 0
Motor Moves limbs purposefully Nonpurposeful movement Not moving
2 1
0
"Modified from Steward (Reference 8)
Patients in the ketamine group received a total of 14 & 8 mg/kg (7.7 2 2.3 mg.kg-'.h-'). Patients in the propofol group received a total of 16 9 mgikg (10 5 4 mg.kg-'.h-'). Recovery from anesthesia, as assessed using the Steward scoring system, was significantly more rapid in the propofol group. The individual Steward scores for complete recovery of consciousness, airway reflexes, and motor function were achieved significantly more rapidly in the propofol group compared with the ketamine group. These data are summarized in Table 3. Linear regression analyses were performed between time to complete recovery (Steward score of 7) and the following parameters: duration of anesthesia, drug dose per kilogram body weight, and drug dose per kilogram body weight per hour. Time to full recovery from ketamine correlated significantly with duration of anesthesia (Y = 0.71, Figure 1) and total ketamine dose per kilogram (r = 0.82, Figure 2). There was no significant correlation, however, between time to full recovery from propofol and duration of anesthesia (r = 0.38) or total propofol dose per kilogram (Y = 0.14). Time to full recovery did not correlate significantly with total drug dose per kilogram per hour in either group. Hemodynamic data are summarized in Table 4. There were no episodes of apnea, airway obstruction, or emesis in any patient, and no interventions were required to treat changes in HR or MAP. However, the number of patients experiencing MAP decreases > 20% (compared to baseline) during induction was significantly higher in the propofol group (P < 0.05). There were no episodes of significant decreases in HR or MAP after induction in either group. Several patients in the ketamine group had episodes of increased HR and MAP, but the frequency of these was not significantly different between the groups. During anesthetic induction, four patients in the propofol group showed arterial desaturations greater
*
492
ANESTH ANALC 1992;74:490-4
PEDIATRIC ANESTHESIA LEBOVIC ET AL CARDIAC CATHETERIZATION ANESTHESIA
Table 2. Demographic Data SPO,
Age
(%)
(W
Weight (kg)
Catheterization duration (min)
93 68
4.6 0.8
20.0 6.8
115 163
88 100 78 91 81 97 85 100
0.6 4.9 2.5 1.1 6.3 0.9 1.0 1.5
4.3 17.6 10.8 5.8 14.0 5.8 10.3
110 65 139 83 55 179 77 95
2.4 t 2.1
10.2 t 5.4
108 ? 41
62 91 99 97
1.1 1.1 5.9 3.1
7.5 7.5 22.7 12.9
130 97 66 79
5
77
1.3
77
187
6 7 8 9 10
88 82 86 100 92
4.0 0.9 5.5 2.8 1.o
14.0 6.6 20.0 15.1 8.2
111 74 113 101 120
2.0
12.2 % 5.7
108 2 35
Ketamine ( n = 10)
Propofol ( I 1 = 10)
132 t 113 t 82 i_ 139 %
24 2 1 9 18 t 11" 17 2 9" 24 2 19''
Patient Ketamine group 1 2 3 4 5 6 7 8 9 10
Mean
5 SD
88
Propofol group 1 2 3 4
Mean
5 SD
87
2
?
10
12
2.7
%
6.4
Diagnosis Tetralogy of Fallot Hypoplastic left side of heart syndromestage I repair Tetralogy of Fallot Ventricular septal defect Ebstein's anomaly Truncus arteriosus, status post repair Tetralogy of Fallot, pulmonary atresia Truncus arteriosus Truncus arteriosus, status post repair Tetralogy of Fallot
Tetralogy of Fallot Tetralogy of Fallot Anomalous left coronary, status post repair Tetralogy of Fallot, status post BlalockTaussig shunt Complex cyanotic heart disease status post Blalock-Taussig shunt Tricuspid atresia Double-outlet right ventricle Pulmonary stenosis, single ventricle Ventricular septal defect Ventricular septal defect
Spo,, digital ox) gen saturation
Table 3. Recoverv Scores
Time to full consciousness (min) Time to airway recovery (min) Time to motor recovery (min) Time to full recovery score (min)
90 65 42 87
Values are mean 2 SD. " P < 0.002, unpaired Student's t-test. "P < 0.001, unpaired Student's t-test
Full Recovery from Ketamine/Midazolam minutes 350
3oo 250
I:
I
-
I -
4
1
la,
A = 0.71
P < 0.05
/
/
4 I
than five percentage points in Spo,, whereas none in the ketamine group showed this degree of change in Spo,. There was no statistically significant relationship (Fisher's exact test) between episodes of desaturation on induction and type of congenital heart defect (i.e., tetralogy of Fallot physiology or direction of primary shunting). All of the episodes of desaturation, however, occurred on induction concomitantly with a transient decrease in blood pressure. There were no arterial desaturations greater than 10 percentage points in either group. Arterial blood gases were obtained during the procedure and demonstrated no statistically significant differences be-
0
L
40
1
_________ 60
60
IW
IM
140
im
180
m
Duration of Anesthetic minutes Figure 1. Linear regression analysis of time to full recovery (score = 7) from ketamineimidazolam with duration of anesthetic.
tween the groups (Table 5). Blood gases were not obtained in all patients mainly because catheterizations of the left side of the heart were not always required. The patients in the propofol group did not experience any myoclonus or thrombophlebitis. There were
1
PEDIATRIC ANESTHESlA LEBOVlC ET AL. CARDIAC CATHETERIZATION ANESTHESlA
ANESTH ANALG 1992;74:49C-4
: !/,//7] Full Recovery from Ketamine minUtes
200 150
/
100
50 0
5
10
15
25
20
40
35
30
Ketamine Dose mg Per kg Figure 2. Linear regression analysis of time to full recovery (score = 7) from ketamineimidazolam with total ketamine dose.
Table 4. Hernodynamic Effects Ketamine Propofol (n = 10) ( n = 10) No. of patients with HR increase > 20% compared with baseline No. of patients with HR decrease > 20% compared with baseline No. of patients with MAP increase > 20% compared with baseline No. of patients with MAP decrease > 20% compared with baseline No. of patients with Spo, decrease > 5 compared with baseline
2
0
0
4
4
0
1
7‘
0
4
HR, heart rate; MAP, mean arterial blood pressure; Spo,, digital oxygen saturation. “ P < 0.05, Fisher’s exact test.
Table 5. Results From Analvsis of Arterial Blood Gases
PHa Paco, (mm Hg) Pao, (mm Hg) HCO,’ (mEqiL) Sao7 (%)
Ketamine ( n = 4)
Propofol (n = 7)
7.37 c 0.01 36 f 4 72 ? 22 21 t 2 92 2 6
7.32 ? 0.03 41 t 5 78 f 24 21 c 2 91 2 7
pHa, arterial pH; Paco,; arterial CO, tension; Pao,, arterial O2 tension; Sao,, arterial oxygen saturation. Values are mean SD.
*
no episodes of emergence delirium or unpleasant dreams in the ketamine group. No postoperative sequelae were reported in either group.
Discussion Ketamine infusions have long been used to produce sedation and analgesia in pediatric patients undergo-
493
ing diagnostic or therapeutic procedures in radiology suites, cardiac catheterization laboratories, burn units, intensive care units, and radiation therapy units (9). However, ketamine is associated with a prolonged recovery period and emergence delirium. In addition, ketamine is often avoided in patients with tachycardia or hypertension, and its effects on pulmonary vascular resistance are controversial (10,ll). Propofol is a new intravenous anesthetic that is noteworthy for rapid emergence. Its use in patients with congenital heart disease has not been previously reported. The results of the current study demonstrate that propofol was associated with markedly shorter recovery times compared with ketamine/midazolam. These results are not surprising considering previous investigations of the recovery characteristics of propofol (2,4) and ketamine (12). The time to complete recovery from ketamineimidazolam correlated with both ketamine dose per kilogram and duration of anesthesia. No such correlations were found in the propofol group. This implies that ketamine/midazolam anesthesia has a cumulative effect, whereas propofol anesthesia does not show this characteristic. The design of the current study was not adequate to speculate on the mechanisms causing this effect. It is important for pediatric patients undergoing cardiac catheterization to remain relatively immobile during the procedure to avoid cardiac perforation, to minimize radiation exposure, and to obtain technically adequate angiograms. Spontaneous movements occur during both ketamine (1) and propofol (13) anesthesia, and they were noted in both groups in the current study. It is difficult to evaluate the incidence and degree of movement in the current study, as this was the criterion for increasing the dose of anesthetic in both groups, and the observers were not blinded to experimental group. It is the authors’ impression, however, that excessive movement was not a problem in either group. A potential disadvantage of propofol infusions is the lack of analgesia at subanesthetic plasma concentrations. Fentanyl was added to the induction dose of propofol in the current study because, in a pilot study, excessive patient movement was noted during infiltration of local anesthetic into the groin. There was a higher incidence ( P < 0.05) of decreased arterial blood pressure during anesthetic induction in the propofol group. These episodes were defined as clinically significant by the study criteria, but tended to be transient and required no therapeutic interventions. The incidence of decreased HR and/or MAP may have been exaggerated by the study criteria because the baseline HR and MAP tended to be elevated in anxious children who had not received preanesthetic medication. It is possible that fentanyl
494
ANESTH ANALG 1992;74:49&4
PEDIATRIC ANESTHESIA LEBOVIC ET AL CARDIAC CATHETERIZATION ANESTHESIA
was partially responsible for the hypotension (14). The only decreases in Spo, occurred in the propofol group. These were mild (>5 percentage points, < l o percentage points) and occurred only during hypotensive episodes associated with anesthetic induction. This suggests that the hemodynamic changes caused by propofol may have increased the right-toleft shunt in some patients. Alternatively, transient respiratory depression could have been the cause. Although no untoward effects occurred after these episodes, the authors believe that it is prudent to avoid propofol in critically ill pediatric patients presenting for cardiac catheterization. The transient decrease in Spo, after anesthetic induction with propofol in the current study contrasts with the results in a similar group of patients studied by Greeley et al. (15). They found that Spo, increased-with both ketamine and halothaneinitrous oxide anesthesia. It is difficult to compare these studies, however, because the patients in Greeley’s study were subjected to inhaled anesthetic inductions or intramuscular injections. These patients may have started with lower than their accustomed Spo, values because of crying or agitation. Benzodiazepines are frequently administered with ketamine to prevent emergence delirium. Midazolam could have prolonged the recovery period in the current study by two mechanisms: a sedative effect that is additive to ketamine or by delaying ketamine’s metabolism (1). In conclusion, propofol infusions with fentanyl analgesia were associated with significantly shorter recovery times than ketamine/midazolam anesthesia in pediatric cardiac catheterization procedures. In addition, propofol anesthesia did not exhibit the cumulative effect seen with ketamine/midazolam. The more rapid emergence associated with propofol may decrease recovery room stays. If overnight hospital stays are avoided with use of the admittedly more expensive propofol anesthetic, then decreased overall costs for ambulatory pediatric patients admitted for cardiac catheterization or similar diagnostic and therapeutic procedures may be realized. Although both anesthetic techniques were satisfactory, propofol anesthesia appears preferable in hemodynamically stable patients with congenital heart dis-
ease admitted for cardiac catheterization, but hypotension may limit the use of propofol in critically ill children. We thank James B. Eisenkraft, manuscript.
MD,
for his critical review of the
References 1. Reich DL, Silvav G. Ketamine: an update on the first 25 years of clinical experience. Can J Anaesth 1989;36:18&97. 2. Skues MA, Prys-Roberts C. The pharmacology of propofol. I CIin Anesth 1989;1:387400. 3. Puttick N, Rosen M. Propofol induction and maintenance with nitrous oxide in paediatric outpatient dental anaesthesia. Anaesthesia 1988;43:646-9. 4. Saint-Maurice C, Cockshott ID, Douglas EJ, Richard MO, Harmev JL. Pharmacokinetics of propofol in young children after a single dose. Br J Anaesth 1989;63:667-70. 5, Patel DK, Keeling PA, Newman GB, Radford P. Induction dose of propofol in children. Anaesthesia 1988;43:949-52. 6. Purcell-Jones G, Yates A, Baker JR, James IG. Comparison of the induction characteristics of thiopentone and propofol in children. Br J Anaesth 1987;59:1431-6. 7. Valtonen M, liaso E, Kanto J, Rosenberg P. Propofol as an induction agent in children: pain on injection and pharmacokinetics. Acta Anaesthesiol Scand 1989;33:152-5. 8 . Steward DJ. A simplified scoring system for the post-operative recovery room. Can Anaesth Soc J 1975;22:111-3. 9. Valtonen M. Anaesthesia for computerised tomography of the brain in children: a comparison of propofol and thiopentone. Acta Anaesthesiol Scand 1989;33:170-3. 10. Wolfe RR, Loehr JP, Schaffer MS, Wiggins JW Jr. Hemodynamic effects of ketamine, hypoxia and hyperoxia in children with surgically treated congenital heart disease residing 21,200 meters above sea level. Am J Cardiol 1991;67:847. 11. Hickey PR, Hansen DD, Cramolini GM, Vincent RN, Lang P. Pulmonary and systemic hemodynamic responses to ketamine in infants with normal and elevated pulmonary vascular resistance. Anesthesiology 1985;62:287-93. 12. White PF, Dworsky WA, Horai Y, Trevor AJ. Comparison of continuous infusion fentanyl or ketamine versus thiopentaldetermining the mean effective serum concentrations for outpatient surgery. Anesthesiology 1983;59:564-9. 13. Borgeat A, Dessibourg C, Popovic V, Meier D, Blanchard M, Schwander D. Propofol and spontaneous movements: an EEG study. Anesthesiology 1991;74:24-7. 11. Van Aken H, Meinshausen E, Prien T, Brussel T, Heinecke A, Lawin P. The influence of fentanyl and tracheal intubation on the hernodynamic effects of anesthesia induction with propofol/N,O in humans. Anesthesiology 1988;68:157-63. 15. Greek? WJ, Bushman GA, Davis DP, Reves JG. Comparative effects of halothane and ketamine on systemic arterial oxygen saturation in children with cyanotic heart disease. Anesthesiology 1986;65:666-8.
MD,
L. Gary Steinberg,
MD,
Frances P. Vela, RN, and
Departments of Anesthesiology and Pediatrics, The Mount Sinai Medical Center, New York, New York
Intravenous propofol was compared with ketamine in 20 pediatric patients undergoing cardiac catheterization. The study patients were randomly assigned to treatment groups so that 10 patients received ketamine and 10 patients received propofol. The hernodynamic responses and recovery characteristics of the two groups were compared. On induction of anesthesia, seven patients in the propofol group experienced a transient decrease in mean arterial blood pressure greater than 20% of baseline accompanied by mild arterial desaturation in four patients. Only one patient in the ketamine group experienced such a decrease in arterial blood pressure. This was the only significant difference ( P < 0.05) in hemodv-
T
he goals for anesthetic management of pediatric patients scheduled to undergo cardiac catheterization include immobility, sedation, and cardiovascular stability. The maintenance of spontaneous ventilation without supplemental oxygen is also desirable so that the normal physiology is least altered by the anesthetic technique. Intravenous ketamine is an agent with a long history of successful use in the cardiac catheterization suite but is associated with hemodynamic aiterations, dysphoric emergence reactions, and a prolonged recovery period (1). Propofol is a substituted phenol anesthetic that is associated with smooth induction of, and rapid recovery from, anesthesia (2). Its pharmacokinetic profile favors administration by continuous intravenous infusion to provide complete anesthesia ( 3 ) .Its safety and efficacy in pediatric patients have been demonstrated in numerous studies (4-6). Reported side effects include pain on injection into small veins (which may be prevented by pretreatment with small doses of intravenous lidocaine) (7) and dose-related decreases in blood pressure and cardiac output. ~
Accepted for publication November 25, 1991. Address correspondence to Dr. Reich, Department of Anesthesiology, Box 1010, The Mount Sinai Medical Center, One Gustave L. Levy Place, New York, NY 10029-6574.
490
Anesth Analg 1992;74:4904
namic effects between the two groups. Time to full recoverv (mean t SD) was significantly less in the propofol group (24 2 19 min vs 139 * 87 min, P < 0.001). In the ketamine group only, significant correlations (I)< 0.05) included time to full recovery with duration of anesthetic ( r = 0.71) and time to full recovery with total drug dose per kilogram (r = 0.82). The authors conclude that propofol anesthesia is a practical alternative for pediatric patients undergoing elective cardiac catheterization and may be preferable to ketamine because of the significantly shorter recoverv time. (Anesth Analg 1992;74:4904)
The current study compared propofol with ketamine for intravenous anesthesia in pediatric patients undergoing cardiac catheterization. This is the first report describing the use of propofol in pediatric patients with congenital heart disease.
Methods After approval of the protocol had been received from the Institutional Review Board, written informed consent was obtained from the parent or guardian. Twenty patients, aged 7 mo to 6 yr, ASA physical status I1 and 111, scheduled for elective cardiac catheterization for evaluation of congenital heart disease were studied. Patients requiring mechanical ventilation or intravenous inotropic support were excluded from the study. No patient received preanesthetic medication, and after a 6-h fast, they arrived in the catheterization laboratory with a n intravenous catheter in situ. The patients were randomly assigned to one of two treatment groups to receive either propofol or ketamine as their anesthetic. Monitoring included a chest stethoscope, electrocardiographic lead 11, a Dinamap blood pressure device, and Nellcor digital pulse oximetry. Heart rate (HR), arterial blood pressure, and preductal digital oxygen saturation (Sp0.J G1992 by
the International Anesthesia Research Society 0003-2999192/$5 00
ANESTH ANALG 1992;74:490-4
were recorded every 5 min for the duration of the study. On arrival in the cardiac catheterization laboratory and after the measurement of baseline Spo, and arterial blood pressure, all patients received glycopyrrolate, 3 pg/kg IV. Patients in the propof01 group received an analgesic dose of fentanyl, 1 pglkg, followed by propofol in 0.5-mgikg boluses every 60 s titrated to an appropriate level of sedation (immobility, tolerance of limb restraints and of preparation of the groin with antiseptic solution). An hourly infusion rate of three times the total induction dose of propofol was administered for maintenance of anesthesia. To decrease the likelihood of pain on injection, the propofol emulsion was diluted 1:l with 5% dextrose solution, and the induction dose was preceded by intravenous lidocaine (0.1 mL/kg of a 0.1% solution). Patients in the ketamine group received ketamine, 2 mgikg, as an intravenous bolus, followed by an infusion of 2 mg.kg-'.h-'. In addition, midazolam, 0.02 mgikg, was administered hourly to prevent emergence delirium. The investigators were not blinded to the experimental groups during the procedure. If patient movement or crying occurred in either group, a bolus of one-half the total induction dose was administered and the infusion rate was increased by 50%. Changes in mean arterial blood pressure (MAP) or HR >20% from awake baseline values were noted. Decreases in digital pulse oximetry (SpoJ >5 points from the awake baseline value were noted. The results of arterial blood gas analyses were recorded whenever they were performed. Anesthetic drug infusions were discontinued when the groin bandage had been applied and the duration of the anesthetic and total drug doses were recorded. Postanesthesia recovery scores, modified from the method of Steward (8), were determined by an independent blinded observer from the time the infusion was stopped until discharge from the recovery room (Table 1). Results are expressed as the mean 2 SD. Data were analyzed using the unpaired Student's t-test, Fisher's exact test, and Pearson's linear regression analysis. Correlation coefficients were compared using Z-transformations. A P value < 0.05 was considered significant.
Results All patients completed the study protocol and no patient required supplemental oxygen. There were no statistically significant differences between the groups with respect to age, weight, duration of catheterization, and baseline Spo, on room air. Demographic data are summarized in Table 2.
PEDIATRIC ANESTHESIA LEBOVIC ET AL. CARDIAC CATHETERIZATION ANESTHESIA
491
Table 1. Recovery Scoring System" Consciousness Awake Responds to verbal stimuli Responds to tactile stimuli Not responding Airway Cough on command or cry Maintains good airway Requires airway assistance
2 1 0
Motor Moves limbs purposefully Nonpurposeful movement Not moving
2 1
0
"Modified from Steward (Reference 8)
Patients in the ketamine group received a total of 14 & 8 mg/kg (7.7 2 2.3 mg.kg-'.h-'). Patients in the propofol group received a total of 16 9 mgikg (10 5 4 mg.kg-'.h-'). Recovery from anesthesia, as assessed using the Steward scoring system, was significantly more rapid in the propofol group. The individual Steward scores for complete recovery of consciousness, airway reflexes, and motor function were achieved significantly more rapidly in the propofol group compared with the ketamine group. These data are summarized in Table 3. Linear regression analyses were performed between time to complete recovery (Steward score of 7) and the following parameters: duration of anesthesia, drug dose per kilogram body weight, and drug dose per kilogram body weight per hour. Time to full recovery from ketamine correlated significantly with duration of anesthesia (Y = 0.71, Figure 1) and total ketamine dose per kilogram (r = 0.82, Figure 2). There was no significant correlation, however, between time to full recovery from propofol and duration of anesthesia (r = 0.38) or total propofol dose per kilogram (Y = 0.14). Time to full recovery did not correlate significantly with total drug dose per kilogram per hour in either group. Hemodynamic data are summarized in Table 4. There were no episodes of apnea, airway obstruction, or emesis in any patient, and no interventions were required to treat changes in HR or MAP. However, the number of patients experiencing MAP decreases > 20% (compared to baseline) during induction was significantly higher in the propofol group (P < 0.05). There were no episodes of significant decreases in HR or MAP after induction in either group. Several patients in the ketamine group had episodes of increased HR and MAP, but the frequency of these was not significantly different between the groups. During anesthetic induction, four patients in the propofol group showed arterial desaturations greater
*
492
ANESTH ANALC 1992;74:490-4
PEDIATRIC ANESTHESIA LEBOVIC ET AL CARDIAC CATHETERIZATION ANESTHESIA
Table 2. Demographic Data SPO,
Age
(%)
(W
Weight (kg)
Catheterization duration (min)
93 68
4.6 0.8
20.0 6.8
115 163
88 100 78 91 81 97 85 100
0.6 4.9 2.5 1.1 6.3 0.9 1.0 1.5
4.3 17.6 10.8 5.8 14.0 5.8 10.3
110 65 139 83 55 179 77 95
2.4 t 2.1
10.2 t 5.4
108 ? 41
62 91 99 97
1.1 1.1 5.9 3.1
7.5 7.5 22.7 12.9
130 97 66 79
5
77
1.3
77
187
6 7 8 9 10
88 82 86 100 92
4.0 0.9 5.5 2.8 1.o
14.0 6.6 20.0 15.1 8.2
111 74 113 101 120
2.0
12.2 % 5.7
108 2 35
Ketamine ( n = 10)
Propofol ( I 1 = 10)
132 t 113 t 82 i_ 139 %
24 2 1 9 18 t 11" 17 2 9" 24 2 19''
Patient Ketamine group 1 2 3 4 5 6 7 8 9 10
Mean
5 SD
88
Propofol group 1 2 3 4
Mean
5 SD
87
2
?
10
12
2.7
%
6.4
Diagnosis Tetralogy of Fallot Hypoplastic left side of heart syndromestage I repair Tetralogy of Fallot Ventricular septal defect Ebstein's anomaly Truncus arteriosus, status post repair Tetralogy of Fallot, pulmonary atresia Truncus arteriosus Truncus arteriosus, status post repair Tetralogy of Fallot
Tetralogy of Fallot Tetralogy of Fallot Anomalous left coronary, status post repair Tetralogy of Fallot, status post BlalockTaussig shunt Complex cyanotic heart disease status post Blalock-Taussig shunt Tricuspid atresia Double-outlet right ventricle Pulmonary stenosis, single ventricle Ventricular septal defect Ventricular septal defect
Spo,, digital ox) gen saturation
Table 3. Recoverv Scores
Time to full consciousness (min) Time to airway recovery (min) Time to motor recovery (min) Time to full recovery score (min)
90 65 42 87
Values are mean 2 SD. " P < 0.002, unpaired Student's t-test. "P < 0.001, unpaired Student's t-test
Full Recovery from Ketamine/Midazolam minutes 350
3oo 250
I:
I
-
I -
4
1
la,
A = 0.71
P < 0.05
/
/
4 I
than five percentage points in Spo,, whereas none in the ketamine group showed this degree of change in Spo,. There was no statistically significant relationship (Fisher's exact test) between episodes of desaturation on induction and type of congenital heart defect (i.e., tetralogy of Fallot physiology or direction of primary shunting). All of the episodes of desaturation, however, occurred on induction concomitantly with a transient decrease in blood pressure. There were no arterial desaturations greater than 10 percentage points in either group. Arterial blood gases were obtained during the procedure and demonstrated no statistically significant differences be-
0
L
40
1
_________ 60
60
IW
IM
140
im
180
m
Duration of Anesthetic minutes Figure 1. Linear regression analysis of time to full recovery (score = 7) from ketamineimidazolam with duration of anesthetic.
tween the groups (Table 5). Blood gases were not obtained in all patients mainly because catheterizations of the left side of the heart were not always required. The patients in the propofol group did not experience any myoclonus or thrombophlebitis. There were
1
PEDIATRIC ANESTHESlA LEBOVlC ET AL. CARDIAC CATHETERIZATION ANESTHESlA
ANESTH ANALG 1992;74:49C-4
: !/,//7] Full Recovery from Ketamine minUtes
200 150
/
100
50 0
5
10
15
25
20
40
35
30
Ketamine Dose mg Per kg Figure 2. Linear regression analysis of time to full recovery (score = 7) from ketamineimidazolam with total ketamine dose.
Table 4. Hernodynamic Effects Ketamine Propofol (n = 10) ( n = 10) No. of patients with HR increase > 20% compared with baseline No. of patients with HR decrease > 20% compared with baseline No. of patients with MAP increase > 20% compared with baseline No. of patients with MAP decrease > 20% compared with baseline No. of patients with Spo, decrease > 5 compared with baseline
2
0
0
4
4
0
1
7‘
0
4
HR, heart rate; MAP, mean arterial blood pressure; Spo,, digital oxygen saturation. “ P < 0.05, Fisher’s exact test.
Table 5. Results From Analvsis of Arterial Blood Gases
PHa Paco, (mm Hg) Pao, (mm Hg) HCO,’ (mEqiL) Sao7 (%)
Ketamine ( n = 4)
Propofol (n = 7)
7.37 c 0.01 36 f 4 72 ? 22 21 t 2 92 2 6
7.32 ? 0.03 41 t 5 78 f 24 21 c 2 91 2 7
pHa, arterial pH; Paco,; arterial CO, tension; Pao,, arterial O2 tension; Sao,, arterial oxygen saturation. Values are mean SD.
*
no episodes of emergence delirium or unpleasant dreams in the ketamine group. No postoperative sequelae were reported in either group.
Discussion Ketamine infusions have long been used to produce sedation and analgesia in pediatric patients undergo-
493
ing diagnostic or therapeutic procedures in radiology suites, cardiac catheterization laboratories, burn units, intensive care units, and radiation therapy units (9). However, ketamine is associated with a prolonged recovery period and emergence delirium. In addition, ketamine is often avoided in patients with tachycardia or hypertension, and its effects on pulmonary vascular resistance are controversial (10,ll). Propofol is a new intravenous anesthetic that is noteworthy for rapid emergence. Its use in patients with congenital heart disease has not been previously reported. The results of the current study demonstrate that propofol was associated with markedly shorter recovery times compared with ketamine/midazolam. These results are not surprising considering previous investigations of the recovery characteristics of propofol (2,4) and ketamine (12). The time to complete recovery from ketamineimidazolam correlated with both ketamine dose per kilogram and duration of anesthesia. No such correlations were found in the propofol group. This implies that ketamine/midazolam anesthesia has a cumulative effect, whereas propofol anesthesia does not show this characteristic. The design of the current study was not adequate to speculate on the mechanisms causing this effect. It is important for pediatric patients undergoing cardiac catheterization to remain relatively immobile during the procedure to avoid cardiac perforation, to minimize radiation exposure, and to obtain technically adequate angiograms. Spontaneous movements occur during both ketamine (1) and propofol (13) anesthesia, and they were noted in both groups in the current study. It is difficult to evaluate the incidence and degree of movement in the current study, as this was the criterion for increasing the dose of anesthetic in both groups, and the observers were not blinded to experimental group. It is the authors’ impression, however, that excessive movement was not a problem in either group. A potential disadvantage of propofol infusions is the lack of analgesia at subanesthetic plasma concentrations. Fentanyl was added to the induction dose of propofol in the current study because, in a pilot study, excessive patient movement was noted during infiltration of local anesthetic into the groin. There was a higher incidence ( P < 0.05) of decreased arterial blood pressure during anesthetic induction in the propofol group. These episodes were defined as clinically significant by the study criteria, but tended to be transient and required no therapeutic interventions. The incidence of decreased HR and/or MAP may have been exaggerated by the study criteria because the baseline HR and MAP tended to be elevated in anxious children who had not received preanesthetic medication. It is possible that fentanyl
494
ANESTH ANALG 1992;74:49&4
PEDIATRIC ANESTHESIA LEBOVIC ET AL CARDIAC CATHETERIZATION ANESTHESIA
was partially responsible for the hypotension (14). The only decreases in Spo, occurred in the propofol group. These were mild (>5 percentage points, < l o percentage points) and occurred only during hypotensive episodes associated with anesthetic induction. This suggests that the hemodynamic changes caused by propofol may have increased the right-toleft shunt in some patients. Alternatively, transient respiratory depression could have been the cause. Although no untoward effects occurred after these episodes, the authors believe that it is prudent to avoid propofol in critically ill pediatric patients presenting for cardiac catheterization. The transient decrease in Spo, after anesthetic induction with propofol in the current study contrasts with the results in a similar group of patients studied by Greeley et al. (15). They found that Spo, increased-with both ketamine and halothaneinitrous oxide anesthesia. It is difficult to compare these studies, however, because the patients in Greeley’s study were subjected to inhaled anesthetic inductions or intramuscular injections. These patients may have started with lower than their accustomed Spo, values because of crying or agitation. Benzodiazepines are frequently administered with ketamine to prevent emergence delirium. Midazolam could have prolonged the recovery period in the current study by two mechanisms: a sedative effect that is additive to ketamine or by delaying ketamine’s metabolism (1). In conclusion, propofol infusions with fentanyl analgesia were associated with significantly shorter recovery times than ketamine/midazolam anesthesia in pediatric cardiac catheterization procedures. In addition, propofol anesthesia did not exhibit the cumulative effect seen with ketamine/midazolam. The more rapid emergence associated with propofol may decrease recovery room stays. If overnight hospital stays are avoided with use of the admittedly more expensive propofol anesthetic, then decreased overall costs for ambulatory pediatric patients admitted for cardiac catheterization or similar diagnostic and therapeutic procedures may be realized. Although both anesthetic techniques were satisfactory, propofol anesthesia appears preferable in hemodynamically stable patients with congenital heart dis-
ease admitted for cardiac catheterization, but hypotension may limit the use of propofol in critically ill children. We thank James B. Eisenkraft, manuscript.
MD,
for his critical review of the
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