Bolus dose with continuous infusion of midazolam as sedation for outpatient surgery
N. H. Luyk, M. Zacharias, S. Wanwimolaruk University of Otago, Dunedin, New Zealand
N. 1t. Luyk, M. Zacharias, S. Wanwimolaruk: Bolus dose with continuous infusion of midazolam as sedation for outpatient surgery. Int. J. Oral Maxillofac. Surg. 1992; 21: 172-175. Abstract. This double-blind, r a n d o m i s e d , cross-over trial in 41 p a t i e n t s for 3rd m o l a r surgery c o m p a r e d the safety, amnesic properties a n d p s y c h o m o t o r recovery between a bolus injection o f m i d a z o l a m a n d a bolus injection followed b y c o n t i n u o u s infusion o f m i d a z o l a m . T h e latter showed g o o d safety a n d better amnesia to events d u r i n g the procedure, b u t p r o l o n g e d the recovery time.
I n t r a v e n o u s m i d a z o l a m has been well established as a suitable sedative a g e n t for use in surgical or o t h e r u n p l e a s a n t procedures under local anaesthesia ~'3'uas. It offers considerable adv a n t a g e s over d i a z e p a m in its amnesic properties, s h o r t e r e l i m i n a t i o n half-life a n d less i r r i t a n t effect o n veins 9, b u t the strong sedative a n d amnesic effects a p p e a r to only last a p p r o x i m a t e l y 20 rain 4,8. U n f o r t u n a t e l y n o t all u n p l e a s a n t procedures last less t h a n 15 m i n a n d a p a t i e n t whose p r o c e d u r e extends bey o n d t h a t p e r i o d m a y n o t b e well sedated. This p r o b l e m c a n be o v e r c o m e b y giving incremental doses o f midazola m or by a c o n t i n u o u s infusion. M i d a z o l a m infusion h a s been recomm e n d e d for c o n t i n u o u s infusion 14. It has been used in intensive care units 2'6 a n d was f o u n d to provide good sedation w i t h o u t p r o d u c i n g significant cardioresp i r a t o r y instability. T h e present trial was designed to study the anxiolytic, sedative, amnesic properties of a b o l u s injection o f m i d a z o l a m followed by cont i n u o u s infusion a n d to observe the psyc h o m o t o r recovery characteristics o f such a technique.
Material and methods Fit, healthy adults (ASAI and II) between the ages of 18 and 40 years with impacted lower 3rd molars, which required surgical removal under local analgesia and intravenous sedation were invited to participate in this study and gave their written consent. Approval of the local Ethics Committee was obtained. Those patients who had taken
benzodiazepines within the past month were excluded from the trial, which was designed as a double-blind, cross-over study. In the immediate preoperative period they were asked to complete a Visual Analogue Scale (0-100) for their anxiety. They also received instructions on, and trim runs of, both Critical Flicker Fusion Threshold (CFFT) and Choice Reaction Time (CRT), followed by recordings of CFFT and CRT, which were the control readings. These tests were used to measure the quality of recovery from the midazolam sedation at the end of the procedure. The CFFT was done using a Leeds Flicker Fusion Tester (Leeds Psychomotor Services, Acomb, York, England) and the CRT was measured using an appropriately designed programme (Mindlab; Courseware Development Group, Dartmouth College, England) on a Macintosh SE computer. Both the infusion used first and the side to be operated on first were determined by random selection. The patient was then seated recumbent in a dental chair and the blood pressure and oxygen saturation were measured using a Dinamap automatic blood pressure monitor and an Oxyshuttle oximeter. An intravenous infusion was started and midazolam was given at a rate of 1 mg/min until clinical sedation was considered achieved when the patient exhibited slurred speech and/or ptosis of the eyelids. A syringe pump (Terumo Corp. Tokyo, Japan) was then used to give a calculated maintenance infusion of either saline or midazolam according to the formula based on that suggested by WHITE14, both for males and females: For males: MIR/~gkg -~ min -~ = LD/zg kg -1 × 8.5 ml min -1 kg -~ 500mlkg -t
Key words: midazolam; sedation; ambulatory surgery Accepted for publication 27 February 1992
For females: MIR/,g kg- l min- 1= LD #g kg- i x 9.0 ml rain- ~kg- 1 700 ml kg l MIR: maintenance infusion rate. LD: loading dose Neither the patient nor the surgeon knew on which occasion the midazolam infusion was given. Local analgesia was administered and the surgery commenced at the onset of analgesia. At 30 rain after the initial injection of midazolam, the surgery was stopped and the patient was shown 2 pictures of easily recognizable objects and were asked to recall the pictures at their routine follow-up appointment. During the entire procedure patients were continuously monitored, the blood pressure and oxygen saturation being recorded at 5-rain intervals. VAS for anxiety was repeated at the completion of the initial dose of midazolam and again at the end of surgery. The surgeon's assessment of the degree of sedation throughout was also recorded on a VAS. The CFFT and CRT were repeated at the end of surgery and again at 30, 60, 90 and 120 min. ~ At 1 week following surgery patients were seen at the usual post-surgical appointment and asked to recall the number of local anaesthetic injections given, the use of the drill and the pictures shown. They rated their degree of sedation as good, satisfactory or poor. Surgery for the opposite side was scheduled at least 2 weeks later, the patient receiving the same bolus dose of midazolam, over the same time period, prior to the commencement of the infusion and the cross-over design was followed. At the final appointment 1 week later patients were also asked during which of the surgeries they felt more relaxed. The results were analysed using Analysis of Variance, Student's t test and Fisher's Ex-
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Acknowledgements. The authors wish to thank Roche Products, New Zealand Ltd., for their contribution to this paper.
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It is concluded that bolus dose, followed by a continuous infusion of midazolam, appears to offer a safe and reliable sedative technique, with improved amnesia, over bolus dose alone, but at the expense of a prolonged impairment of psychomotor functions.
References
1. BROPHYT, DUNDEE JW~ HEAZELWOODV, -7
!
Control
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End TEST
3'0 TIMES
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90
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(MINUTES)
Fig. 2. Critical Flicker Fusion Threshold versus Test Times. * p
N. H. Luyk, M. Zacharias, S. Wanwimolaruk University of Otago, Dunedin, New Zealand
N. 1t. Luyk, M. Zacharias, S. Wanwimolaruk: Bolus dose with continuous infusion of midazolam as sedation for outpatient surgery. Int. J. Oral Maxillofac. Surg. 1992; 21: 172-175. Abstract. This double-blind, r a n d o m i s e d , cross-over trial in 41 p a t i e n t s for 3rd m o l a r surgery c o m p a r e d the safety, amnesic properties a n d p s y c h o m o t o r recovery between a bolus injection o f m i d a z o l a m a n d a bolus injection followed b y c o n t i n u o u s infusion o f m i d a z o l a m . T h e latter showed g o o d safety a n d better amnesia to events d u r i n g the procedure, b u t p r o l o n g e d the recovery time.
I n t r a v e n o u s m i d a z o l a m has been well established as a suitable sedative a g e n t for use in surgical or o t h e r u n p l e a s a n t procedures under local anaesthesia ~'3'uas. It offers considerable adv a n t a g e s over d i a z e p a m in its amnesic properties, s h o r t e r e l i m i n a t i o n half-life a n d less i r r i t a n t effect o n veins 9, b u t the strong sedative a n d amnesic effects a p p e a r to only last a p p r o x i m a t e l y 20 rain 4,8. U n f o r t u n a t e l y n o t all u n p l e a s a n t procedures last less t h a n 15 m i n a n d a p a t i e n t whose p r o c e d u r e extends bey o n d t h a t p e r i o d m a y n o t b e well sedated. This p r o b l e m c a n be o v e r c o m e b y giving incremental doses o f midazola m or by a c o n t i n u o u s infusion. M i d a z o l a m infusion h a s been recomm e n d e d for c o n t i n u o u s infusion 14. It has been used in intensive care units 2'6 a n d was f o u n d to provide good sedation w i t h o u t p r o d u c i n g significant cardioresp i r a t o r y instability. T h e present trial was designed to study the anxiolytic, sedative, amnesic properties of a b o l u s injection o f m i d a z o l a m followed by cont i n u o u s infusion a n d to observe the psyc h o m o t o r recovery characteristics o f such a technique.
Material and methods Fit, healthy adults (ASAI and II) between the ages of 18 and 40 years with impacted lower 3rd molars, which required surgical removal under local analgesia and intravenous sedation were invited to participate in this study and gave their written consent. Approval of the local Ethics Committee was obtained. Those patients who had taken
benzodiazepines within the past month were excluded from the trial, which was designed as a double-blind, cross-over study. In the immediate preoperative period they were asked to complete a Visual Analogue Scale (0-100) for their anxiety. They also received instructions on, and trim runs of, both Critical Flicker Fusion Threshold (CFFT) and Choice Reaction Time (CRT), followed by recordings of CFFT and CRT, which were the control readings. These tests were used to measure the quality of recovery from the midazolam sedation at the end of the procedure. The CFFT was done using a Leeds Flicker Fusion Tester (Leeds Psychomotor Services, Acomb, York, England) and the CRT was measured using an appropriately designed programme (Mindlab; Courseware Development Group, Dartmouth College, England) on a Macintosh SE computer. Both the infusion used first and the side to be operated on first were determined by random selection. The patient was then seated recumbent in a dental chair and the blood pressure and oxygen saturation were measured using a Dinamap automatic blood pressure monitor and an Oxyshuttle oximeter. An intravenous infusion was started and midazolam was given at a rate of 1 mg/min until clinical sedation was considered achieved when the patient exhibited slurred speech and/or ptosis of the eyelids. A syringe pump (Terumo Corp. Tokyo, Japan) was then used to give a calculated maintenance infusion of either saline or midazolam according to the formula based on that suggested by WHITE14, both for males and females: For males: MIR/~gkg -~ min -~ = LD/zg kg -1 × 8.5 ml min -1 kg -~ 500mlkg -t
Key words: midazolam; sedation; ambulatory surgery Accepted for publication 27 February 1992
For females: MIR/,g kg- l min- 1= LD #g kg- i x 9.0 ml rain- ~kg- 1 700 ml kg l MIR: maintenance infusion rate. LD: loading dose Neither the patient nor the surgeon knew on which occasion the midazolam infusion was given. Local analgesia was administered and the surgery commenced at the onset of analgesia. At 30 rain after the initial injection of midazolam, the surgery was stopped and the patient was shown 2 pictures of easily recognizable objects and were asked to recall the pictures at their routine follow-up appointment. During the entire procedure patients were continuously monitored, the blood pressure and oxygen saturation being recorded at 5-rain intervals. VAS for anxiety was repeated at the completion of the initial dose of midazolam and again at the end of surgery. The surgeon's assessment of the degree of sedation throughout was also recorded on a VAS. The CFFT and CRT were repeated at the end of surgery and again at 30, 60, 90 and 120 min. ~ At 1 week following surgery patients were seen at the usual post-surgical appointment and asked to recall the number of local anaesthetic injections given, the use of the drill and the pictures shown. They rated their degree of sedation as good, satisfactory or poor. Surgery for the opposite side was scheduled at least 2 weeks later, the patient receiving the same bolus dose of midazolam, over the same time period, prior to the commencement of the infusion and the cross-over design was followed. At the final appointment 1 week later patients were also asked during which of the surgeries they felt more relaxed. The results were analysed using Analysis of Variance, Student's t test and Fisher's Ex-
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174
Luylc et al. •
1
MIDAZOLAM SAUNE
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Acknowledgements. The authors wish to thank Roche Products, New Zealand Ltd., for their contribution to this paper.
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It is concluded that bolus dose, followed by a continuous infusion of midazolam, appears to offer a safe and reliable sedative technique, with improved amnesia, over bolus dose alone, but at the expense of a prolonged impairment of psychomotor functions.
References
1. BROPHYT, DUNDEE JW~ HEAZELWOODV, -7
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Control
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3'0 TIMES
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90
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(MINUTES)
Fig. 2. Critical Flicker Fusion Threshold versus Test Times. * p
