Efficacy of two oral premedicants: midazolam or a low‐dose combination of midazolam–ketamine for reducing stress during intravenous cannulation in children undergoing CT imaging

Background: Pain, anxiety and fear of needles make intravenous cannulation extremely difficult in children. We assessed the efficacy and safety of oral midazolam and a low‐dose combination of midazolam and ketamine to reduce the stress and anxiety during intravenous cannulation in children undergoing computed tomography (CT) imaging when compared to placebo. Methods: Ninety‐two ASA I or II children (1–5 years) scheduled for CT imaging under sedation were studied. Children were randomized to one of the three groups. Group M received 0.5 mg·kg^?1 midazolam in 5 ml of honey, group MK received 0.25 mg·kg^?1 midazolam mixed with 1 mg·kg^?1 ketamine in 5‐ml honey and group P received 5‐ml honey alone, orally. In 20–30 min after premedication, venipuncture was attempted at the site of eutectic mixture of local anesthetics cream. Sedation scores and venipuncture scores were recorded. Primary outcome of the study was incidence of children crying at venipuncture (venipuncture score of 4). Results: Significantly more children cried during venipuncture in placebo group compared to the other two groups (19/32 (59%) in group P vs 1 each in groups M and MK, (P < 0.001) (RR 2.37, 95% CI 1.55‐3.63). In 20–30 min after premedication, group P had more children in sedation score 1 or 2 (crying or anxious) compared to the other two groups (P < 0.05). At this time, group MK showed more children in calm and awake compared to group M (P = 0.02). At venipuncture, group P had more children in venipuncture score 3 or 4 (crying or withdrawing) compared to group M or MK (P < 0.05), while groups M and MK were comparable. Conclusion: A low‐dose combination of oral midazolam and ketamine or oral midazolam alone effectively reduces the stress during intravenous cannulation in children undergoing CT imaging without any adverse effects. However, the combination provides more children in calm and quiet state when compared to midazolam alone at venipuncture.     

Two doses of oral ketamine,given with midazolam,for premedication in children

BACKGROUND: Oral premedication is common practice in paediatric anaesthesia. The aim of this study was to assess the quality of premedication using oral ketamine, with midazolam. METHODS: Clinical randomized and blind-study on 120 patients, aged between 2 and 6 years, listed for minor surgery. Patients were divided in three groups: first group (group MK1) received midazolam and ketamine at the doses of 0.3 mgxkg-1 and 1 mgxkg-1, respectively; the second (group MK2) received 0.3 mgxkg-1 of midazolam and 2 mgxkg-1 of ketamine; the control group 0.5 mgxkg-1 of midazolam (group M). Success of premedication was assessed by assigning 1-4 points to the quality of anxiolysis and sedation every 5 min after drug administration and then at the moment of separation from parents, entrance to theatre and response to mask induction of general anaesthesia. RESULTS: More patients were successfully premedicated in the MK2 group, statistical significance was observed after 20 min (p<0.05). The MK2 group accepted separation from parents (p<0.05) and face mask for induction of anaesthesia (p<0.05) more willingly. Side effects were observed in 4 MK2 group patients (nausea, headache and diplopia), but all these effects resolved spontaneously. CONCLUSIONS: Two mgxkg-1 of ketamine given orally with midazolam improve anxiolysis and sedation and achieve more success of premedication, better acceptance of parental separation and better acceptance of face mask for induction of anaesthesia.     

Premedication with intramuscular midazolam: effect on induction time with intravenous midazolam compared to intravenous thiopentone or ketamine

Our study sought to determine whether premedication with intramuscular midazolam would decrease the time to induction of anaesthesia with intravenous midazolam, and if so whether induction of anaesthesia would be as rapid as with thiopentone or ketamine, intravenously. Eight-nine patients, ASA physical status I or II, received midazolam 0.2 mg X kg-1, thiopentone 3.0 mg X kg-1, or ketamine 2.0 mg X kg-1 intravenously 60-90 min after intramuscular injection of either midazolam 0.07 mg X kg-1 or matching placebo. Time to induction of anaesthesia or the dose required to induce anaesthesia with intravenous midazolam was not decreased by midazolam premedication. Both with or without premedication, midazolam induction time was longer than with thiopentone or ketamine. Midazolam induction was associated with a lower incidence of blood pressure increase than with ketamine induction, and a lower incidence of apnea than that with either thiopentone or ketamine.     

Oral ketamine or midazolam or low dose combination for premedication in children

This randomized controlled trial was designed to evaluate whether the combination of low dose oral midazolam (0.25 mg/kg) and low dose oral ketamine (3 mg/kg) provides better premedication than oral midazolam (0.5 mg/kg) or oral ketamine (6 mg/kg). Seventy-eight children of ASA physical status I or II scheduled for elective ophthalmic surgery were randomly divided into three groups and given premedication in the holding area 30 minutes before surgery. Two subjects from each group vomited the medication and were excluded, leaving 72 subjects for further analysis. The onset of sedation was earlier in the combination group than the other two groups. At 10 minutes after premedication 12.5% in the combination group had an acceptable sedation score compared with none in the other two groups. After 20 minutes 54% in the combination group had an acceptable sedation score, 21% in the midazolam group and 16% in the ketamine group (P<0.05). There were no significant differences in the parental separation score, response to induction and emergence score. The mean time for best parental separation score was significantly less in the combination group (19+/-8 min) than either the midazolam (28+/-7) or ketamine (29+/-7 min) groups (P<0.05). Recovery was earlier in the combination group, as the time required to reach a modified Aldrete score of 10 was significantly less in the combination group (22+/-5 min) than in the oral midazolam (36+/-11 min) or ketamine (38+/-8 min) groups. The incidence of excessive salivation was significantly higher in the ketamine alone group (P<0.05). In conclusion, the combination of oral ketamine (3 mg/kg) and midazolam (0.25 mg/kg) has minimal side effects and gives a faster onset and more rapid recovery than ketamine 6 mg/kg or midazolam 0.5 mg/kg for premedication in children.     

Oral preanaesthetic medication for children: double-blind randomized study of a combination of midazolam and ketamine vs midazolam or ketamine alone

Anxiolysis and sedation with oral midazolam are common practice in paediatric anaesthesia. However, good or excellent results are seen in only 50-80% of cases. For this reason, we investigated if addition of a low dose of oral ketamine (MIKE: ketamine 3 mg kg-1, midazolam 0.5 mg kg-1) resulted in better premedication compared with oral midazolam 0.5 mg kg-1 or ketamine 6 mg kg-1 alone, in a prospective, randomized, double-blind study. We studied 120 children (mean age 5.7 (range 2-10) yr) undergoing surgery of more than 30 min duration. After oral premedication in the ward and transfer, the child's condition in the induction room was evaluated by assigning 1-4 points to the quality of anxiolysis, sedation, behaviour at separation from parent and during venepuncture (transfer score). On days 1 and 7 after operation, parents were interviewed for changes in behaviour (eating, sleep, dreams, toilet training), recollection and satisfaction, using a standardized questionnaire. The groups were similar in age, sex, weight, intervention and duration of anaesthesia. The transfer score was significantly better in the MIKE group (12.5 (95% confidence interval (CI) 11.9-13.1)) than in the ketamine or midazolam groups (10.6 (9.8- 11.4) and 11.5 (10.7-12.3), respectively). Success rates for anxiolysis and behaviour at separation were greater than 90% with the combination, approximately 70% with midazolam and only 51% with ketamine alone. The incidence of salivation, excitation and psychotic symptoms was low in all groups. Vertigo and emesis before induction were significantly more frequent after ketamine premedication. During recovery, there were no differences in sedation or time of possible discharge. After 1 week, parents reported nightmares (ketamine five, midazolam three, MIKE one), restless sleep (five/four/four) or negative memories (three/four/one). There were no major or continuing disturbances in behaviour or development. In summary, significantly better anxiolysis and separation were observed with a combination of ketamine and midazolam, even in awake children (sedation was not successful according to the preset criteria), than with midazolam or ketamine alone. Duration of action and side effects of the combination were similar to those of midazolam. The combination of both drugs in strawberry flavoured glucose syrup (pH 4.5 approximately) is chemically stable for 8 weeks.      

Midazolam (Dormicum) as oral premedication for local anesthesia

Good physician-patient rapport and an anxiolytic, sedative, and amnesic premedication are necessary for comfortable, stress-free surgery under local anesthesia. Sufficient experience exists with the intramuscular and intravenous administration of the new benzodiazepine midazolam (Dormicum), while knowledge relating to its oral administration is still scant. Therefore, in a randomized double-blind study midazolam was investigated for oral premedication prior to local anesthesia: two dosages of midazolam were studied and compared with diazepam and placebo. One hour prior to ophthalmic surgery under local anesthesia, four randomized groups of 30 patients each, received a tablet of 7.5 or 15 mg midazolam, 10 mg diazepam, or a placebo. Following this medication, the anxiolytic, sedative, amnesic, and side-effects were determined at defined points of time during the day of surgery and the 1st postoperative day. Anxiolysis was determined using the "state-trait anxiety inventory (STAI)" of Spielberger et al.; sedation was assessed according to Pandit et al.; amnesia was determined by recall of picture cards which had been presented to the patients 50 min after premedication; and patients were asked about 13 side-effects typical of benzodiazepines in a standardized way. Anxiety increased little following the placebo; it decreased significantly following 10 mg diazepam and more markedly following 7.5 and 15 mg midazolam. Sedation increased little following the placebo; it increased more and similarly 50 min after the benzodiazepines; after 90 min the sedative effect was most marked for 15 mg midazolam. However, sedation was of shorter duration after midazolam than after diazepam.(ABSTRACT TRUNCATED AT 250 WORDS)     

A randomised placebo-controlled trial of the effects of midazolam premedication on children's postoperative cognition

This randomised, placebo-controlled study assessed the effects of midazolam premedication on children's postoperative cognition and physical morbidity. In all, 179 children aged 5-10 years were randomly assigned to receive buccal midazolam (0.2 mg x kg(-1)) or placebo before sevoflurane-nitrous oxide anaesthesia for multiple dental extractions. They performed tests of choice reaction time, attention, psychomotor co-ordination and memory pre-operatively (baseline), before discharge and at 48 h. The reaction time of both groups was significantly slower before discharge compared to baseline, with the midazolam group being significantly slower than placebo. Psychomotor co-ordination was also significantly impaired postoperatively after midazolam. Performance on both tests had recovered to baseline by 48 h. Midazolam was also associated with significant anterograde amnesia, both postoperatively and at 48 h, for information presented in the interval between premedication and surgery. The results show significant short-term impairment of children's cognitive function and amnesia enduring for 48 h after low-dose midazolam premedication.     

Oral premedication with midazolam in paediatric anaesthesia. Effects on sedation and gastric contents

The aim of this study was to assess oral premedication with midazolam in paediatric anaesthesia. Sedation, quality of induction, recovery time, acceptance and effects on gastric contents were analysed. This prospective, double blind, at random and controlled study was performed in 107 children, aged between three and ten years. They were divided into: group 1 (control, n=29), group 2 (placebo) receiving 5 ml of water in the preoperative stage (n=40), and group 3 (midazolam) with 0.75 mg·kg^-1 midazolam by mouth (n=38). Two children refused to take medication. In children aged five years or more (n=48) of groups 2 and 3, acceptance of premedication was evaluated. The midazolam group showed a better level of sedation as compared with the placebo (P<0.05). The recovery time was similar for the two groups. There were no statistically significant differences in gastric pH or residual volume among the three groups. It is concluded that midazolam given by mouth is an efficient and safe drug for premedication in paediatric anaesthesia.     

Preoperative alprazolam reduces anxiety in ambulatory surgery patients: a comparison with oral midazolam

Because an oral formulation of midazolam is not approved in certain countries, we evaluated oral alprazolam as an alternative. Forty-five outpatients scheduled for gynecological laparoscopic surgery participated in a double-blinded study to compare the effectiveness and side effects of oral alprazolam 0.5 mg with midazolam 7.5 mg, as a reference drug, and placebo. We evaluated psychomotor function by means of the Trieger Dot Test (TDT) and the Digit-Symbol Substitution Test. Simple memory tests were performed. Data were analyzed with chi(2) or paired Student's t-tests, or with one-way analysis of variance with the Student-Newman-Keuls or Kruskal-Wallis test, as appropriate; P < 0.05 was considered statistically significant. Alprazolam and midazolam both decreased anxiety scores more than placebo (P < 0.05). One hour after premedication, the Digit- Symbol Substitution Test score was similar in all groups, whereas the TDT score was greater (indicating impairment of performance) in the alprazolam group than in the placebo group (P < 0.05). Sedation scores, extubation time, and discharge times in the active drug groups did not differ from placebo. At discharge from the postanesthesia care unit, the TDT score was greater in both active drug groups compared with placebo (P < 0.05). Five patients, exclusively in the midazolam group, had amnesia (P < 0.05). We conclude that alprazolam may be an effective alternative to midazolam for anxiety reduction without causing amnesia. However, it may cause greater impairment of psychomotor function in the early postoperative period. IMPLICATIONS: Oral alprazolam 0.5 mg and midazolam 7.5 mg comparably reduce anxiety in ambulatory surgery patients. Despite early psychomotor impairment, neither drug delays postanesthetic extubation nor prolongs discharge from the postanesthesia care unit.     

Reevaluation of Rectal Ketamine Premedication in Children: Comparison with Rectal Midazolam

Background: Results of previous studies of rectal ketamine as a pediatric premedication are clouded because of lack of dose-response relation, inappropriate time of assessing sedative effects, and previous administration or coadministration of benzodiazepines. Therefore, the authors reevaluated the efficacy of rectally administered ketamine in comparison with 1 mg/kg rectal midazolam.

Methods: Sixty-six infants and children (age, 7-61 months) who were American Society of Anesthesiologists physical status I and who were undergoing minor surgeries as in-patients were randomized to receive 5 mg/kg ketamine (n = 16), 7 mg/kg ketamine (n = 16), 10 mg/kg ketamine (n = 17), or 1 mg/kg midazolam (n = 17) via rectum. A blinded observer scored sedation 45 min and 15 min after administration of ketamine and midazolam, respectively, when children were separated from parent(s) for inhalational induction. All children underwent standardized general anesthesia with sevoflurane, nitrous oxide, and oxygen with endotracheal intubation. Blood pressure, heart rate, and oxyhemoglobin saturation were determined before, during, and after anesthesia. Postoperative recovery characteristics and incidence of adverse reactions were also assessed.

Results: Most children (88%) who received rectally 10 mg/kg ketamine or 1 mg/kg midazolam separated easily from their parents compared with those (31%) who received 7 or 5 mg/kg rectal ketamine (P < 0.05). Similarly, more children who received 10 mg/kg ketamine or 1 mg/kg midazolam underwent mask induction without struggling or crying compared with those who received 7 or 5 mg/kg ketamine (P < 0.05). There were no clinically significant changes in blood pressure, heart rate, and oxyhemoglobin saturation after administration of either drug. Immediately after surgery, more children receiving midazolam or 5 mg/kg ketamine were agitated compared with 7 or 10 mg/kg ketamine. Ketamine, 7 and 10 mg/kg, provided postoperative analgesia, but the largest dose of ketamine was associated with delayed emergence from general anesthesia.     

Dexmedetomidine Premedication Attenuates Ketamine-induced Cardiostimulatory Effects and Postanesthetic Delirium

Background: Dexmedetomidine is a new potent and highly selective alpha2 -adrenoceptor agonist with sedative-hypnotic and anesthetic sparing properties. Because of its sympathoinhibitory activity, it may prove useful in balancing the cardiostimulalory effects and attenuating the adverse central nervous system effects of ketamine.

Methods: A double-blind, randomized and comparative parallel-group study design was employed in 40 volunteers with ASA physical status 1 who were scheduled for elective superficial surgery under ketamine anesthesia. Dexmedetomidine (2.5 micro gram/kg, n = 20) or midazolam (0.07 mg/kg, n = 20) was administered intramuscularly 45 min before induction of anesthesia. Anesthesia was induced with 2 mg/kg ketamine intravenously, and muscle relaxation was achieved with vecuronium. After tracheal intubation, anesthesia was maintained with nitrous oxide/oxygen (2:1) and additional 1 mg/kg intravenous ketamine boluses according t clinical and cardiovascular criteria. Hypotension and bradycardia were treated by increasing the intravenous infusion rate of crystalloids and intravenous atropine, respectively. Sedative and anxiolytic properties, intra- and postoperative drug requirements, psychomotor and cognitive impairments, and cardiovascular effects were compared between the two groups.

Results: Dexmedetomidine and midazolam proved to have equal sedative and anxiolytic effects after intramuscular administration, but dexmedetomidine induced significantly less preoperative psychomotor impairment and less anterograde amnesia than did midazolam. Compared to midazolam, dexmedetomidine decreased the need for intraoperative ketamine and was more effective in reducing ketamine-induced adverse central nervous system effects. Dexmedetomidine also was superior to midazolam in attenuating the hemodynamic responses to intubation and the cardiostimulatory effects of ketamine in general, but it increased the incidence of intra and postoperative bradycardia.     

A comparison of two different doses of ketamine with midazolam and midazolam alone as oral preanaesthetic medication on recovery after sevoflurane anaesthesia in children

BACKGROUND: This investigation prospectively evaluated the effect of oral premedication of two different doses of ketamine with midazolam and midazolam alone on the recovery of children after sevoflurane anaesthesia. METHODS: In a randomized, double-blind study, 79 children (aged 1-8 years, ASA physical status I or II) were assigned to receive one of three premedications in a volume of 0.5 ml x kg(-1): group 1 received midazolam 0.5 mg x kg(-1) (MD); group 2 received midazolam 0.5 mg x kg(-1) with ketamine 1.8 mg x kg(-1) (MK-1); and group 3 received midazolam 0.5 mg x kg(-1) with ketamine 3 mg x kg(-1) (MK-2). The reactions of the children during administration were noted. Anaesthesia was induced by facemask with incremental sevoflurane administration. All children received alfentanil (15 micro g x kg(-1)). Tracheal intubation was facilitated by mivacurium (0.2 mg x kg(-1)). Anaesthesia was maintained with sevoflurane and an additional dose of alfentanil, if necessary. During recovery, the time interval between discontinuation of anaesthesia and arousal (spontaneous ventilation, extubation) were recorded. RESULTS: Emergence (spontaneous ventilation, extubation) and recovery times (discharge, Aldrete score=9) did not differ significantly between groups (P=0.24, P=0.59 and P=0.145, respectively). CONCLUSIONS: The combination of midazolam and ketamine as oral preanaesthetic medication did not significantly affect the recovery time of children after sevoflurane anaesthesia.     

The action of S-(+)-ketamine on serum catecholamine and cortisol. A comparison with ketamine racemate]

The S(+)-isomer of ketamine has about twice the anaesthetic potency of the commercially available racemic mixture of ketamine. It is assumed that the known side-effects of ketamine are significantly reduced when administering half the usual dose with the same pharmacodynamic effect [17, 25]. The aim of the present study was to determine the haemodynamic effects, the catecholamine and cortisol plasma levels after administration of equally potent doses of S-(+)-Ketamine and racemic mixture of ketamine. In addition, the effect of premedication with i.v. midazolam was assessed. METHOD. After approval by the ethics committee and written informed consent, 30 healthy male volunteers were randomly allocated to three groups (n = 10). Group 1 received 2 mg/kg ketamine racemate, group 2 1 mg/kg S-(+)-Ketamine, and group 3 1 mg/kg S-(+)-Ketamine 5 min after i.v.-premedication with 0.1 mg/kg midazolam. Non-invasive blood pressure (BP) and heart rate (HR) were continuously recorded. Blood samples were drawn 7 min before, and 2, 4, 8, 16, 32, 64 and 128 min after drug administration. Plasma epinephrine and norepinephrine (NE) levels were determined by HPLC and cortisol plasma levels by RIA. Data were analysed with the Kruskal-Wallis test (P < or = 0.05) for differences between groups. RESULTS. HR and BP showed a significant rise after injection of racemate and isomer, without any significant differences between groups. This was also seen for norepinephrine and cortical plasma levels. Epinephrine levels, however, differed between groups, showing a significant rise after racemate compared to isomer. Premedication with midazolam, in contrast, blunted major haemodynamic and hormonal changes. DISCUSSION. The haemodynamic changes did not differ between the racemate and isomer group despite a reduced isomer dose. HR and BP rise were similar, although epinephrine levels were significantly lower after isomer than racemate. Hence we assume that the increase in the haemodynamic parameters were mainly caused by NE. Midazolam apparently prevented the centrally mediated sympathetic stimulation caused by ketamine and its isomers. Therefore, i.v. premedication with midazolam should be applied when racemate or isomer is used, especially in high-risk cardiac patients.     

Perioperative effects of melatonin and midazolam premedication on sedation, orientation, anxiety scores and psychomotor performance

BACKGROUND AND OBJECTIVE: To compare the perioperative effects of melatonin and midazolam given in premedication, on sedation, orientation, anxiety scores and psychomotor performance. METHODS: Exogenous administration of melatonin not only facilitates the onset of sleep but also improves its quality. A prospective, randomized, double-blind, placebo-controlled study was performed in 66 patients undergoing laparoscopic cholecystectomy. Patients were given melatonin 5 mg, midazolam 15 mg or placebo, 90 min before anaesthesia, sublingually. Sedation, orientation and anxiety were quantified before; 10, 30, 60 and 90 min after premedication; and 15, 30, 60 and 90 min after admission to the recovery room. Neurocognitive performance was evaluated at these times, using the Trail Making A and B and Word Fluency tests. The differences between the groups were analysed by ANOVA. Two-way comparisons were performed by Scheffé analysis. Sedation and amnesia were analysed by the chi2 test. RESULTS: Patients who received premedication with either melatonin or midazolam had a significant increase in sedation and decrease in anxiety before operation compared with controls. After operation, there was no difference in sedation scores of all groups. Whereas, 30, 60 and 90 min after premedication the melatonin and midazolam groups exhibited a significantly poorer performance in Trail Making A and B tests compared with placebo, there were no significant differences among the groups in terms of neuropsychological performance after the operation. Amnesia was notable only in the midazolam group for one preoperative event. CONCLUSION: Melatonin premedication was associated with preoperative anxiolysis and sedation without postoperative impairment of psychomotor performance.     

Reevaluation of rectal ketamine premedication in children: comparison with rectal midazolam

BACKGROUND: Results of previous studies of rectal ketamine as a pediatric premedication are clouded because of lack of dose-response relation, inappropriate time of assessing sedative effects, and previous administration or coadministration of benzodiazepines. Therefore, the authors reevaluated the efficacy of rectally administered ketamine in comparison with 1 mg/kg rectal midazolam. METHODS: Sixty-six infants and children (age, 7-61 months) who were American Society of Anesthesiologists physical status I and who were undergoing minor surgeries as in-patients were randomized to receive 5 mg/kg ketamine (n = 16), 7 mg/kg ketamine (n = 16), 10 mg/kg ketamine (n = 17), or 1 mg/kg midazolam (n = 17) via rectum. A blinded observer scored sedation 45 min and 15 min after administration of ketamine and midazolam, respectively, when children were separated from parent(s) for inhalational induction. All children underwent standardized general anesthesia with sevoflurane, nitrous oxide, and oxygen with endotracheal intubation. Blood pressure, heart rate, and oxyhemoglobin saturation were determined before, during, and after anesthesia. Postoperative recovery characteristics and incidence of adverse reactions were also assessed. RESULTS: Most children (88%) who received rectally 10 mg/kg ketamine or 1 mg/kg midazolam separated easily from their parents compared with those (31%) who received 7 or 5 mg/kg rectal ketamine (P < 0.05). Similarly, more children who received 10 mg/kg ketamine or 1 mg/kg midazolam underwent mask induction without struggling or crying compared with those who received 7 or 5 mg/kg ketamine (P < 0.05). There were no clinically significant changes in blood pressure, heart rate, and oxyhemoglobin saturation after administration of either drug. Immediately after surgery, more children receiving midazolam or 5 mg/kg ketamine were agitated compared with 7 or 10 mg/kg ketamine. Ketamine, 7 and 10 mg/kg, provided postoperative analgesia, but the largest dose of ketamine was associated with delayed emergence from general anesthesia. CONCLUSIONS: The results indicate that rectally administered ketamine alone produces dose-dependent sedative effects in children, when evaluated at its predicted peak plasma concentration. Ketamine, 10 mg/kg, has a delayed onset but is as effective as 1 mg/kg midazolam for sedating healthy children before general anesthesia. However, 10 mg/kg rectal ketamine is not recommended for brief surgeries because of prolonged postoperative sedation.     

Midazolam used for premedication reinforces sleep induced by flunitrazepam

This single blind study aimed to discover possible effects of intramuscular premedication with midazolam on the sleep induced by intravenous flunitrazepam. 24 male patients, aged 17 to 71 years, who were to undergo surgery to the distal parts of an upper limb under regional anaesthesia, were randomly assigned to two equal groups: in the midazolam group, an intramuscular premedication of 0.12 mg.kg-1 midazolam with 0.5 mg atropine was given, whereas in the control group atropine only was used. In all patients, 1 mg flunitrazepam was given intravenously 45 min after the premedication, before carrying out regional anaesthesia. No other drug was given. In the midazolam group, the time of loss of spontaneous conversation was reduced (p less than 0.05), as well as the time of eye closure (p less than 0.001), and the time for recovery of the capacity to count backwards was increased (p less than 0.001). So, premedication with 0.12 mg.kg-1 midazolam intravenously 45 min before giving 1 mg flunitrazepam reinforced the sleep induced by the latter.     

Analgosedierungsverfahren für zahnärztlich-chirurgische Eingriffe mit Midazolam/Pentazocin und Midazolam/Ketamin Klinische Doppelblindstudie zu Anxiolyse,Analgesie, Sedierung und Amnesie

Ketamine and midazolam, applied as intravenous medication for conscious sedation in day-case maxillo-facial surgery, has been proven to be superior to pentazocine and midazolam concerning cardiovascular parameters and respiratory depression. The aim of this study was to evaluate the effects of low-dose ketamine/midazolam on anxiety, analgesia, amnesia and subjective feelings. Methods. 140 out-patients (ASA I) were randomly divided into four groups. The double-blind study was prospective. Control group: Local anaesthesia (LA), articaine 4% plus epinephrine 1:200000 (n=35); test group P/M: LA, additional pentazocine 0.40 mg/kg bw and midazolam 0.075 mg/kg bw i.v. (n=35); test group K25/M: LA, additionally ketamine 0.25 mg/kg bw and midazolam 0.075 mg/kg bw i.v. (n=35), test group K50/M: LA, additionally ketamine 0.5 mg/kg bw and midazolam 0.075 mg/kg bw i.v. (n=35). LA was injected 3 min after application of the systemic medication in the test groups or application of a placebo (saline 0.9%) in the control group. Three further minutes later, operation was started. For evaluation questionnaires, visual analogue scales (VAS) and the state-trait anxiety inventory (STAI) were used. For testing retrograde and anterograde amnesia, acoustic sensations were delivered before application of the systemic medication (a Christmas carol) and during operation (the German national anthem). Results. The control group and the test groups were comparable with regard to biological data, duration of operation, applied dosage of local anaesthetics and actual anxiety before operation. The patients in all test groups rated intraoperative anxiety as mild, in contrast to the control group. Nearly no pain sensation during the operation was remembered in all test groups. Retrograde amnesia was not found in any group. Complete anterograde amnesia was observed in all test groups with respect to the intraoperative sensation, but even in the control group 50% of the patients did not remember having heard the national anthem. As subjective feelings negative criteria were mainly reported in the control group, where as in all test groups positive sensations dominated. Dreams were reported mostly after the higher dosage of ketamine, but no patient experienced any unpleasant dreams. The clinical assessment of the different regimes were excellent for test groups P/M and K50/M, modest for the control group and test group K25/M. Postoperatively, patients of test group P/M were remarkably sedated, but no clinically relevant sedation or motor weakness were observed in the other groups. Postoperative pain sensations were rated more intense in all test groups than in the control group. In test groups P/M and K25/M an increasing pain level was recorded during the postoperative period, with the consequence of a higher demand rate for analgesics. Conclusions. Dental surgery can be performed safely with low-dose ketamine/midazolam. Compared to pentazocine/midazolam, the higher dosage of ketamine (0.5 mg/kg bw) showed identical results intraoperatively, but was superior during the postoperative period (vigilance), and thus may represent a suitable dosage. The lower dosage of ketamine resulted in worse operating conditions, but a dosage higher than 0.5 mg/kg bw might lead to unconscious sedation and might increase the frequency of unpleasant dreams.     

Premedication with melatonin: a double-blind, placebo-controlled comparison with midazolam

We have evaluated the perioperative effects of melatonin with those of midazolam in 75 women in a prospective, randomized, double-blind, placebo-controlled study. Patients were given sublingual midazolam 15 mg, melatonin 5 mg or placebo, approximately 100 min before a standard anaesthetic. Sedation, anxiety and orientation were quantified before, and 10, 30, 60 and 90 min after premedication, and 15, 30, 60 and 90 min after admission to the recovery room. Psychomotor performance was evaluated at these times also, using the digit-symbol substitution test (DSST) and the Trieger dot test (TDT). Patients who received premedication with either midazolam or melatonin had a significant decrease in anxiety levels and increase in levels of sedation before operation compared with controls. Midazolam produced the highest scores for sedation at 30 and 60 min after administration and significant psychomotor impairment in the preoperative period compared with melatonin or placebo. After operation, patients who received midazolam or melatonin premedication had increased levels of sedation at 30 min and impairment in performance on the DSST at 15, 30 and 90 min compared with controls. There were no significant differences between the three groups for anxiety levels or TDT performance after operation. Amnesia was notable only in the midazolam group for one preoperative event (entry into the operating room). Patient satisfaction was noted in the midazolam and melatonin groups only. We have demonstrated that melatonin can be used effectively for premedication of adult patients.      

Premedication of children with oral midazolam

In a randomized, double-blind, placebo-controlled study, the safety, efficacy and feasibility of oral midazolam premedication in children were evaluated in an ambulatory surgery unit. Eighty unmedicated children (ASA PS I or II, ages 1-6 yr) were randomly assigned to one of four groups receiving midazolam 0.5, 0.75, or 1.0 mg.kg-1 or a placebo 30 min before separation from parents. Heart rate, systolic blood pressure, arterial oxygen saturation, respiratory rate, sedation and anxiolysis scores were recorded before premedication, every five minutes for 30 min and then during induction of anaesthesia and recovery. We found that heart rate, systolic blood pressure, arterial oxygen saturation and respiratory rate were unchanged during the study. Sedation and anxiolysis scores in the midazolam-treated groups were greater than those in the placebo group and that anxiolysis at the time of separation from the parents was judged excellent in 80-90% of the children who received midazolam. However, sedation and anxiolysis did not differ among the three midazolam groups. Mean times to discharge from hospital were similar for all four groups. The side effects, loss of balance and head control, blurred vision and dysphoric reactions were observed only in the 0.75 and 1.0 mg.kg-1 midazolam groups. We conclude that oral midazolam 0.5 mg.kg-1 is a safe and effective premedication and that 0.75 and 1 mg.kg-1 while offering no additional benefit, may cause more side effects.     

The effect of skin surface warming on pre-operative anxiety in neurosurgery patients

Skin surface warming of patients not only improves thermal comfort, but has been shown to reduce anxiety in a pre-hospital setting. We tested the hypothesis that pre-operative warming can reduce pre-operative anxiety as effectively as a conventional dose of intravenous midazolam in patients undergoing neurosurgery. We randomly allocated 80 patients to four groups in the pre-operative holding area. Treatment was applied for 30-45 min with (1) passive insulation and placebo; (2) passive insulation and intravenous midazolam (30 microg.kg-1); (3) warming with forced-air and placebo; and (4) warming with forced-air and intravenous midazolam (30 microg.kg-1). Thermal comfort levels (VAS 0-100 mm) and anxiety levels (VAS 0-100 mm, Spielberger State-Trait Anxiety Inventory) were assessed twice: before the designated treatment was started and before induction of anaesthesia. In the midazolam and the midazolam/warming groups, anxiety VAS and Spielberger state anxiety scores decreased by -19 (95% CI: -29 to -9, p<0.01) and -10 (95% CI: -14 to -6, p<0.01), respectively. In the warming and the combined groups, thermal VAS increased by +26 (95% CI: 17-34, p<0.01). Pre-operative warming did not reduce anxiety VAS (p=0.11) or Spielberger state anxiety (p=0.19). The results of our study indicate that pre-operative warming can be recommended solely to improve thermal comfort, not to replace anxiolytic premedication regimens.