Ketamine-midazolam Combination Research Articles

Comparison of the hemodynamic effects of etomidate-midazolam and ketamine-midazolam combinations in anesthesia induction in coronary artery bypass surgery

Aims: We aimed to compare the effects of anesthesia induction on hemodynamic parameters of ketamine-midazolam or etomidate-midazolam combinations and coronary artery bypass grafting surgery.
 Material and Methods: 40 adult patients undergoing CABG were randomly allocated into two groups for this prospective randomized double-blinded study. Ketamine group (n = 20) and Etomidate group (n = 20). Intraoperative and postoperative hemodynamic variables, adrenal gland functions and intensive care period were compared after anesthesia induction with etomidate and ketamine.
 Results: Perioperative hemodynamic parameters were not significantly different between the groups. Despite similar baseline measurements, cortisol levels were significantly higher 5 minutes after induction, during rewarming, and after ACTH stimulation test at postoperative day 1 in group ketamine than group etmidate. The groups were not significantly different in terms of duration of postoperative mechanical ventilation, frequency of postoperative delirium, and intensive care unit and hospital lengths of stay.
 Conclusion: Ketamine-midazolam combination is an acceptable alternative to etomidate-midazolam combination in terms of hemodynamic stability. Compared with the ketamine-midazolam combination, the etomidate-midazolam combination significantly decreased cortisol levels during the intraoperative and early postoperative periods

Evaluation of Efficacy of Oral Ketamine and Midazolam Combination Drug in Different Doses in Different Groups Used for Moderate Sedation in Pediatric Dentistry Randomized-comparative Trial

BackgroundDental phobia and apprehension in children lead to difficulty with behavior management. During dental procedure if a child had a bad experience, he will develop greater apprehension, which makes further treatment difficult.Aim and objectiveThe aim and objective of the present study is to assess and compare the sedation and wake-up behavior status of oral combinations of three different doses of ketamine and midazolam drugs in three different groups mixed in 1 mL of honey.MethodologyThis study was a randomized, clinical study that included patients ranging from 3 to 9 years of age with American Society of Anesthesiologists–I status with carious teeth, were randomly allocated among three groups where group (A) received 0.2 mg/kg of oral midazolam and 5 mg/kg oral ketamine combination drugs, group (B) received 0.3 mg/kg of oral midazolam with 3 mg/kg of oral ketamine combination drugs and group (C) received 0.4 mg/kg of oral midazolam with 2 mg/kg of oral ketamine combination drugs mixed in 1 mL of honey.Child patient's who fulfilled the inclusion criteria, heart rate, blood pressure, and oxygen saturation was recorded from starting of the treatment until discharged from the monitoring room. Ease of treatment completion was evaluated according to the Houpt scale, patients’ behavior, sedation, and wake-up behavior status were evaluated with modified observer assessment of alertness and sedation scale (MOAAS).ResultsIn the study, various doses of ketamine-midazolam combination drugs in three different groups resulted in a clement increase in heart rate, systolic blood pressure (SBP), and diastolic blood pressure (DBP) during the procedure but variations among the groups were not significant. As per MOAAS, the sedation success rate in group B (83.3%) was more than group A (66.6%) and group C (66.6%).All the three groups equally showed the same i.e., (91.6%), behavior score during treatment. Ease of treatment completion was excellent in group B (83.3%) followed by group A and group C [i.e.], (66.7%). Whereas, wake-up behavior score as per MOAAS scale was found to be calm and cooperative in group B (91.7%) followed by group C (88.9%) and group A (83.3%).ConclusionIn the present study oral ketamine-midazolam combination drugs can be used without harm and effectively as moderate sedation in an uncooperative pediatric patient.How to cite this articleThakur S, Verma K, Singhal P, et al. Evaluation of Efficacy of Oral Ketamine and Midazolam Combination Drug in Different Doses in Different Groups Used for Moderate Sedation in Pediatric Dentistry Randomized-comparative Trial. Int J Clin Pediatr Dent 2021;14(S-2):S151–S156.

The Effects of Ketamin-Midazolam and Ketamin-Propofol on Bispectral Index Score as Sedatives During Bone Marrow Puncture Procedure Among Pediatrics

Background: Bone Marrow Puncture (BMP) is an invasive procedure associated with pain and anxiety. The ketamine-midazolam and the ketamine-propofol is an effectivecombination with minimal side effects. This study of the study aims to compare the effect of the combination of ketamine-midazolam and ketamine- propofol on sedation depth based on BIS in pediatric leukemia patients undergoing BMP.
 Methods: This study was a randomized controlled trial that was done single-blinded. The population was all pediatric patients diagnosed with leukemia who underwent BMP at RSMH and performed sedation. The research sample is the population that fulfill the inclusion and exclusion criteria. The sample size for each group was 25, with 50 Subjects in total. Sampling was done by block randomization.
 Results: This study found no differences in sex, age, and body weight between the two groups ([p=1.000], [p=0.845], and [p=0.147], respectively). In this study, there was no difference in mean MAP (p=0.592), oxygen saturation (p=0.164), heart rate (p=0.098), and respiratory rate (p=0.252) before intervention between the two groups. BIS value of the two groups had significant difference before and after the intervention where the two groups could reduce BIS to reach the optimal value of sedation <60 (p <0.05) There was no difference in BIS before intervention in the two groups (p=0.385). In this study, it was found that hypersalivation occurred more frequently in the ketamine-midazolam combination group.
 Conclusion: The combination of ketamine-midazolam and ketamine-propofol was equally good for sedation as indicated by a decrease in the mean BIS in patients undergoing BMP.

Treatment of acetylcholinesterase inhibitor-induced seizures with polytherapy targeting GABA and glutamate receptors

The initiation and maintenance of cholinergic-induced status epilepticus (SE) are associated with decreased synaptic gamma-aminobutyric acid A receptors (GABAAR) and increased N-methyl-d-aspartate receptors (NMDAR) and amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR). We hypothesized that trafficking of synaptic GABAAR and glutamate receptors is maladaptive and contributes to the pharmacoresistance to antiseizure drugs; targeting these components should ameliorate the pathophysiological consequences of refractory SE (RSE). We review studies of rodent models of cholinergic-induced SE, in which we used a benzodiazepine allosteric GABAAR modulator to correct loss of inhibition, concurrent with the NMDA antagonist ketamine to reduce excitation caused by increased synaptic localization of NMDAR and AMPAR, which are NMDAR-dependent. Models included lithium/pilocarpine-induced SE in rats and soman-induced SE in rats and in Es1−/− mice, which similar to humans lack plasma carboxylesterase, and may better model soman toxicity. These model human soman toxicity and are refractory to benzodiazepines administered at 40 min after seizure onset, when enough synaptic GABAAR may not be available to restore inhibition. Ketamine-midazolam combination reduces seizure severity, epileptogenesis, performance deficits and neuropathology following cholinergic-induced SE. Supplementing that treatment with valproate, which targets a non-benzodiazepine site, effectively terminates RSE, providing further benefit against cholinergic-induced SE. The therapeutic index of drug combinations is also reviewed and we show the improved efficacy of simultaneous administration of midazolam, ketamine and valproate compared to sequential drug administration. These data suggest that future clinical trials should treat both the lack of sufficient inhibition and the excess excitation that characterize RSE, and include early combination drug therapies.This article is part of the special issue entitled ‘Acetylcholinesterase Inhibitors: From Bench to Bedside to Battlefield’.

A comparison of ketamine-midazolam combination and propofol-fentanyl combination on procedure comfort and recovery process in pediatric colonoscopy procedures.

Objective:To compare the efficacy and safety of midazolam-ketamine combination versus fentanyl-propofol combination in pediatric diagnostic colonoscopy.Methods:This is a retrospective study of 68 children undergoing diagnostic gastroenterology with midazolam-ketamine combination (Group-K) or with fentanyl-propofol combination (Group-P) in the pediatric gastroentology department at a Turkish tertiary hospital between January 2015 and June 2017. An intravenous midazolam was administered one minute before ketamine administration in Group K. Intravenous fentanyl was given to Group P, followed by intravenous propofol.Results:There were statistically no significant differences between the groups as for age, gender, weight, duration of colonoscopy and complications observed during procedure. Ramsay sedation score was significantly higher in Group K. Recovery time and the rate of complications during the recovery of Group-K (23 patients, 65.7%) was significantly higher than that of Group P (8 patients, 24.2%) (p= 0.001).Conclusions:Colonoscopy procedures can be quite comfortable in children when using the midazolam-ketamine combination. However, adverse effects related to ketamine were observed during recovery.

Ketamine–propofol versus ketamine–midazolam for procedural sedation and analgesia in children with hematological malignancies: a randomized, open-labeled, cross-over trial

Background The use of procedural sedation and analgesia for painful procedures in children with hematological malignancies has become a standard practice in recent time. We compared the occurrence of hypoxia, apnea, and pain between ketamine–propofol and ketamine–midazolam combination. Patients and methods This randomized, open-labeled cross-over study was conducted in 60 children aged 1–15 years scheduled for bone marrow aspiration and, or intrathecal chemotherapy. They were divided into two groups of 30 to receive either ketamine–propofol or ketamine–midazolam. Sedation was performed by trained anesthetists according to the study protocol. Data were analyzed with independent t-test, χ2-test and Fisher’s exact test. P value 0.05 or less was considered significant. Results A total of 120 procedures were performed. One (1.7%) patient in each group had hypoxia, (P=0.8). The oxygen saturation decreased to 83 and 88% in ketamine–propofol and ketamine–midazolam groups, respectively. This was accompanied by bradycardia with a heart rate of 56 and 58 beats/min, respectively. Both events responded to oxygen therapy. There was no episode of apnea, and all maintained spontaneous respiration. The number of patients with a pain score of at least 5 during the procedure was comparable; ketamine–propofol group [6 (10%)] versus ketamine–midazolam group [4 (6.7%)] (P=0.4). Hallucinations were more common in the ketamine–propofol group [4(6.7%)] than the ketamine–midazolam group [0 (0%)] (P=0.05). Conclusion The occurrence of hypoxia, apnea, and pain was comparable following the administration of ketamine–propofol and ketamine–midazolam combination.

Comparison of ketamine with midazolam versus ketamine with fentanyl for pediatric extracorporeal shock wave lithotripsy procedure: A randomized controlled study

Objectives:To compare the effects of ketamine-fentanyl (KF) and ketamine-midazolam (KM) combinations on hemodynamic parameters, recovery properties, pain, and side effects in pediatric patients undergoing extracorporeal shock wave lithotripsy (ESWL) procedure.Methodology:In this double-blinded, randomized trial, 60 pediatric patients aged between 1 and 13 years with American Society of Anesthesiologists physical status Classes I and II, who scheduled for ESWL procedure, were included in the study. Patients were randomly divided into two groups: Group KM received 0.1 mg/kg of midazolam +1–1.5 mg/kg of ketamine and Group KF received 1 μg/kg of fentanyl +1–1.5 mg/kg of ketamine intravenously.Results:There were similar demographic properties, recovery, and discharge times between groups. No statistically significant difference was found in peripheral oxygen saturation, mean and diastolic blood pressure, Ramsey sedation scores, modified Aldrete recovery scores, side effects, and recovery times (Group KM, 16.067 ± 1.2 min; Group KF, 19.46 ± 0.86 min) between groups (P > 0.05).Conclusion:KF combination offers better hemodynamic properties, less side effects with lower visual analog scores, and face, legs, activity, cry, and consolability scores than KM in the pediatric ESWL procedure.

A Comparative Evaluation of the Sedative Effects of Nitrous Oxide-oxygen Inhalation and Oral Midazolam-Ketamine Combination in Children.

AimsTo compare nitrous oxide-oxygen inhalation and low dose oral midazolam-ketamine combination for anxiolysis in the management of children aged between 3 to 10 years for dental treatment.Materials and methodsA comparative clinical study with equal number of subjects in both the groups evaluating efficacy of oral ketamine-midazolam combination and nitrous oxide-oxygen inhalation in children with Frankl behavior rating score 2 and ASA1.A total of 30 children were equally divided into 2 groups, oral midazolam-ketamine (MK) group which received 0.25mg/ kg midazolam with 3mg/kg ketamine in combination and the Nitrous oxide-oxygen (N) group which received nitrous oxide-oxygen inhalation. The parameters evaluated were the drug/ mask acceptance, need for the use of a physical restraint. Houpt’s sedation scale, faces pain score, sedation duration, time taken to achieve the maximum sedation and adverse reactions were assessed. Student t-test was used for comparison between the groups and proportions were compared using Chi-square test.ResultsThe results found no statistically significant differences between the groups in all the parameters except for the duration of sedation and the time taken to achieve maximum sedation which were higher in oral MK group than the Nitrous-oxide oxygen inhalation group.ConclusionBoth oral-midazolam and ketamine combination and nitrous oxide-oxygen inhalation sedation were found to have similar clinical success among 3 to 10-year-old children in bringing about anxiolysis during dental treatment.Clinical SignificanceBoth oral ketamine-midazolam combination, nitrous oxide-oxygen inhalation are equally effective for anxiolysis in children during dental treatment.How to cite this article: Ilasrinivasan, Setty JV, Shyamachalam, Mendiretta P. A Comparative Evaluation of the Sedative Effects of Nitrous Oxide-oxygen Inhalation and Oral Midazolam-Ketamine Combination in Children. Int J Clin Pediatr Dent., 2018;11(5):399-405.

Does ketamine-midazolam combination act as a routine and safe chemical restraint in cats? Clinical and hemato-biochemical evaluation

Intramuscular administration of ketamine-midazolam was used as a fast-acting chemical restraint, with convenient use of the drug in domestic cats. Furthermore, biochemical and hematological changes were evaluated following administration. A total of 20 clinically healthy cats were selected. During the physical examination, cephalic vein was prepared aseptically. Then, cats were restrained cautiously and intravenous catheter was placed in the cephalic vein and immediately heparinized. After covering and protecting the catheter, the animals were kept in separate cages for half an hour. Subsequently, the first blood samples were obtained before intramuscular injection of combination of ketamine and midazolam. The intervals between injection and animal sedation were recorded and the second blood samples were taken. Results showed that the interval between intramuscular injection compound and clinical sedation, the time of second sampling, was 6 ± 2.12 (mean ± SD) min and cat’s recovery time and the time of returning to full power, consciousness, and ability to move and balance were recorded 19 ± 5.35 (mean ± SD) min. Also, values of blood-biochemical parameters were measured before and after administration of the ketamine-midazolam combination and implications on the effect of subsequent administration of the compound on the RBC count, hemoglobin values, PCV, WBC count, lymphocyte percentile, and glucose levels which were found to be significantly reduced (P < 0.05). It seemed that using a combination of ketamine-midazolam could well be tolerated in restraining cats without clinical complications. Following administration of this combination, a short time induction of clinical sedation is a valuable finding that may help to discharge clinical cases without undue delay.

Comparative study between the effect of sevoflurane and ketamine-midazolam on the cardiac troponin I level and hemodynamic variables in pediatric therapeutic cardiac catheterization for pulmonic stenosis

Introduction Congenital pulmonary stenosis is considered one of the most common cardiac anomalies in pediatrics. Percutaneous balloon dilatation is one method for its treatment, but it is usually associated with an increase in the cardiac troponin level. Aims and objectives The study was carried out to compare between the effect of sevoflurane and ketamine-midazolam on the level of cardiac troponin I as a specific marker for myocardial injury in children before and after therapeutic cardiac catheterization for pulmonic stenosis. Patients and methods Forty patients, up to 13 years old, undergoing cardiac catheterization were divided randomly into two groups: sevoflurane group (Gs) and ketamin-midazolam group (Gk-m). The standardized protocol for cardiac catheterization was maintained for all the patients. Serum samples were withdrawn at the start of - and 6 h subsequent to - the procedure for analysis of cardiac troponin I. Hemodynamic and oxygenation parameters were recorded at induction, T10, T20, and T30 minutes after induction. After recovery, sedation was assessed using the Ramsay Sedation Score. Results Hemodynamic parameters, mean arterial blood pressure, heart rate, and cardiac index were significantly increased in Gk-m as compared with its basal values and with Gs. The serum cardiac troponin I was significantly increased after the procedure in both groups as compared with its basal value before the procedure. The increase in the cardiac troponin I was significantly higher in Gk-m than Gs ( P < 0.001). The Ramsay Sedation Score showed a significant increase in Gk-m than Gs at all times postoperatively. Conclusion The use of sevoflurane as an anesthetic regimen for pediatric therapeutic cardiac catheterization for pulmonic stenosis is superior to the ketamine-midazolam combination as it is associated with a lower troponin I level, less myocardial injury, and greater hemodynamic stability.

Comparison of intranasal and intramuscular ketamine-midazolam combination in cats

ObjectiveThe aim of the present study was to compare intranasal (INS) and intramuscular (IM) routes of administration of a ketamine-midazolam combination in cats. Study designRandomized block design. AnimalsTwelve healthy mixed breed cats (six males and six females). MethodsThe drug combination was ketamine (14 mg kg−1) and midazolam (0.5 mg kg−1). In the IM group, drugs were injected into quadratus femoris muscle; in the INS. group, the combination dropped equally into the two nostrils. Pulse and respiratory rates, peripheral haemoglobin oxygen saturation (SpO2) and rectal temperature were monitored before and at intervals after drug administration. Time to onset and duration of sedation and, during recovery to head up, sternal recumbency and recovery were recorded. ResultsThere were no significant differences between the groups in any time measured except for recovery to sternal recumbency, where time was lower in the INS than in the IM (p = 0.034). Respiratory rate was greater in the INS than in the IM group (p = 0.029), but there was no difference between groups in other physiological parameters. In both groups SpO2 was low before and fell further during sedation. ConclusionsThe results substantiated that INS ketamine-midazolam can produce effective sedation in cats. Clinical relevanceIntranasal (INS) administration of ketamine-midazolam is atraumatic, and its use may avoid the pain of injection of ketamine combinations when this drug is used to induce sedation in cats.

De invloed van romifidine en detomidine op de inductie en recovery bij paarden in combinatie met totale intraveneuze anesthesie

In de voorliggende studie werd de kwaliteit van de inductie en de recovery vergeleken bij 146 paarden na totale intraveneuze anesthesie met guaifenesine, ketamine en detomidine, ten behoeve van computertomografie (CT). Ze werden willekeurig ingedeeld, waarbij de ene groep romifidine (n=110) en de andere groep detomidine (n=36) als premedicatie kreeg. De anesthesie werd geïnduceerd met een combinatie van ketamine/midazolam. De gemiddelde anesthesieduur van de CT was kort (gemiddeld +/- SD: 23,5 +/- 8,8 minuten). Er bleek geen significant verschil te zijn voor de inductiescore. Wel bleken paarden gepremediceerd met romifidine een significant betere recoveryscore te hebben.

The Effect of Ketamine-Midazolam and Remifentanil-Midazolam on Sedation, Recovery and Hemodynamic in Pediatric Cardiac Catheterization

The Effect of Ketamine-Midazolam and Remifentanil-Midazolam on Sedation, Recovery and Hemodynamic Parametres in Pediatric Cardiac CatheterizationObjective: The purpose of this study was to compare the effects of ketamine-midazolam and remifentanil-midazolam combinations on hemodynamic, sedation and recovery levels in pediatric cardiac catheterization patients who received anesthesia. Material and Methods: One hundred ASA II-III pediatric patients between ages of 3 months and 10 years, scheduled for cardiac catheterization between June 2011 and August 2011 were randomly allocated into 2 equal (n=50) study groups assigned to receive sedation with ketamine (1 mgkg) (Group I) or remifentanil (0.1 mgkgmin ) infusions (Group II). Patients requiring mechanical ventilation and intravenous inotropic support were excluded from the study analysis. Before induction of anesthesia, patients were transferred to the cardiac catheterization laboratory and their electrocardiograms (ECG) and oxygen saturation (SpO) levels were continuously measured. Before premedication, all patients were monitored and their blood pressures (NIBP) were measured with an noninvasive method, and sedation scores according to Modified Ramsey Sedation Scale (MRSS). recorded Both groups initially received midazolam 0.05-0.1 mgkg for premedication. After catheterization anaesthetic medications of the patients were stopped, and they were sent to recovery room where their hemodynamic data and recovery scores were recorded.Results: Both groups demonstrated similar demographic characteristics. However, Patients received remifentanilmidazolam infusion reported significantly lower heart rate and mean blood pressure values compared to patients who received ketamine-midazolam. Hypotension with bradycardia were observed in these patients. There was no significant difference between the two groups in terms of MRS scores, duration of anesthesia ve process time. However, the recovery time of the patients in Group I was significantly longer than Group II. Conclusion: In this study, we have concluded that the infusion of remifentanil-midazolam combination provides a satisfactory sedation, and shorter recovery time.as an alternative to ketamine used routinely in pediatric cardiac catheterization

The Role of a Low-Dose Ketamine-Midazolam Regimen in the Management of Severe Painful Crisis in Patients With Sickle Cell Disease

ContextAcute pain is one of the main causes of hospital admission in sickle cell disease, with variable intensity and unpredictable onset and duration. ObjectivesWe studied the role of a low-dose intravenous (IV) ketamine-midazolam combination in the management of severe painful sickle cell crisis. MethodsA retrospective analysis was performed with data from nine adult patients who were admitted to the intensive care unit with severe painful sickle cell crises not responding to high doses of IV morphine and other adjuvant analgesics. A ketamine-midazolam regimen was added to the ongoing opioids as an initial bolus of ketamine 0.25mg/kg, followed by infusion of 0.2–0.25mg/kg/h. A midazolam bolus of 1mg followed by infusion of 0.5–1mg/h was added to reduce ketamine emergence reactions. Reduction in morphine daily requirements and improvement in pain scores were the determinants of ketamine-midazolam effect. The t-tests were used for statistical analysis. ResultsNine patients were assessed, with mean age of 27±11 years. Morphine requirement was significantly lower after adding the IV ketamine-midazolam regimen. The mean±SD IV morphine requirement (milligram/day) in the pre-ketamine day (D0) was 145.6±16.5, and it was 112±12.2 on Day 1 (D1) of ketamine treatment (P=0.007). The Numeric Rating Scale scores on D0 ranged from eight to ten (mean 9.1), but improved to range from five to seven (mean 5.7) on D1. There was a significant improvement in pain scores after adding ketamine-midazolam regimen (P=0.01). ConclusionLow-dose ketamine-midazolam IV infusion might be effective in reducing pain and opioid requirements in patients with sickle cell disease with severe painful crisis. Further controlled studies are required to prove this effect.

The effects of ketamine-midazolam anesthesia on intraocular pressure in clinically normal dogs

To determine the effects of intravenous ketamine-midazolam anesthesia on intraocular pressure (IOP) in ocular normotensive dogs. Thirteen adult mixed-breed dogs. Dogs were randomly assigned to treatment (n = 7) and control (n = 6) groups. Dogs in the treatment group received intravenous ketamine 15 mg/kg and midazolam 0.2 mg/kg and dogs in the control group received intravenous saline. The time of intravenous drug injection was recorded (T(0)). Measurements of IOP were then repeated 5 min (T(5)) and 20 min (T(20)) following the intravenous administration of ketamine-midazolam combination and saline in both groups. Measurements showed normal IOP values in both groups. The mean + or - SD baseline IOP values for treatment and control groups were 13.00 + or - 1.47 and 10.33 + or - 2.20, respectively. For baseline IOP values, there was no significant difference between treatment and control groups (P = 0.162). In the treatment group, the subsequent post-treatment mean + or - SD values were 15.64 + or - 2.17 (5 min), and 14.92 + or - 1.98 (20 min). There was no evidence of statistical difference between baseline values and post-treatment values after treatment with ketamine-midazolam (P(5) = 0.139; P(20) = 0.442). In control eyes, the mean + or - SD values at 5 and 20 min were 10.41 + or - 2.01 and 10.16 + or - 1.69, respectively. There was no significant difference between baseline values and post-treatment values in control group (P(5) = 1.000; P(20) = 1.000). Ketamine-midazolam combination has no clinically significant effect on IOP in the dog.

Sedation with intravenous ketamine and midazolam for painful procedures in children

Children often require relief of pain and anxiety when undergoing painful procedures. The purpose of this study is to evaluate the effectiveness and safety of painful pediatric procedures performed by pediatric intensivist, using the combination of intravenous ketamine and midazolam for sedation and analgesia. The records of the patients who received intravenous ketamine-midazolam combination for painful procedures in the pediatric sedation unit of a university hospital over a 3 year period were retrospectively reviewed to determine indications, dosing, assessment of the level of sedation, adverse events, and recovery time for each procedural sedation and analgesia. A total of 227 children aged 4 months to 18 years were admitted to the pediatric sedation unit for a total of 356 procedures. The indications for procedural sedation and analgesia included bone marrow aspiration or biopsy (50.8%), central venous catheter insertion (27%), and others (22%). A total of 46 adverse events (12.9%) were observed. These adverse events included SpO2 below 85% without apnea (n = 14), apnea (n = 3), transient stridor (n = 2), hypertension and tachycardia (n = 8), hypersalivation (n = 6), vomiting (n = 5), hallucinatory emergence reaction (n = 4), and rash (n = 4). There were no adverse outcomes attributable to ketamine and midazolam combination. Skilled pediatric intensivists can safely and effectively administer ketamine and midazolam to facilitate painful procedures outside the operating room setting.

Chronobiological Study of the Pharmacological Response of Rats to Combination Ketamine–Midazolam

Ketamine is commonly administered in combination with benzodiazepines to achieve surgical anaesthesia in rats. The aim of the present study was to analyze the pharmacological response of the combination ketamine–midazolam injected intraperitoneally at different times of day to rats. The study was conducted in July 2003, during the winter in the Southern hemisphere. Female prepuberal Sprague-Dawley rats synchronized to a 12 h light:12 h dark cycle (light, 07:00–19:00 h) were used as experimental animals. A combination treatment of ketamine (40 mg/kg) and midazolam (2 mg/kg) was administered to five different clock-time groups of rats (n = 7/group). Duration of the latency period, ataxia, loss-of-righting reflex (LRR), post-LRR ataxia, and total pharmacological response were assessed by visual assessment. Significant treatment-time differences were detected in the duration of LRR, post-LRR ataxia, and total pharmacological response duration. The longest pharmacological response occurred in rats injected during the light (rest) phase, and the shortest pharmacological response occurred in rats injected during the dark (activity) phase. Cosinor analysis documented circadian rhythmicity in the duration of post-LRR ataxia. The findings of the study indicate the duration of CNS-depression of the ketamine–midazolam combination exhibits treatment-time-dependent variation in the rat.

Cardiorespiratory effects of induction and maintenance of anesthesia with ketamine-midazolam combination, with and without prior administration of butorphanol or oxymorphone

Summary Cardiorespiratory effects of an iv administered bolus of ketamine (7.5 mg/kg of body weight) and midazolam (0.375 mg/kg) followed by iv infusion of ketamine (200 μg/kg/min) and midazolam (10 μg/kg/min) for 60 minutes was determined in 6 dogs. Ketamine-midazolam combination was administered to dogs on 3 occasions to determine effects of prior administration of iv administered saline solution (1 ml), butorphanol (0.2 mg/kg), or oxymorphone (0.1 mg/kg). The infusion rate of ketamine and midazolam was decreased by 25% for anesthetic maintenance after opioid administration. There were no significant differences in cardiorespiratory variables after saline solution or butorphanol administration; however, oxymorphone caused significant (P &lt; 0.05) increases in mean arterial blood pressure, systemic vascular resistance, and breathing rate. Bolus administration of ketamine-midazolam combination after saline solution caused significant (P &lt; 0.05) increases in heart rate, mean arterial blood pressure, cardiac index, mean pulmonary blood pressure, venous admixture, and significant decreases in stroke index, pulmonary capillary wedge pressure, arterial and mixed venous oxygen tension, arterial oxygen content, and alveolar-arterial oxygen gradient. Opioid administration was associated with significantly (P &lt; 0.05) lower values than was saline administration for heart rate, mean arterial blood pressure, and arterial and mixed venous pH and with higher values for stroke index, pulmonary capillary wedge pressure, and arterial and mixed venous carbon dioxide tension. Prior oxymorphone administration resulted in the highest (P &lt; 0.05) values for mean pulmonary blood pressure, venous admixture, and arterial and mixed venous carbon dioxide tension, and the lowest values for arterial oxygen tension, and arterial and mixed venous pH. Each treatment provided otherwise uncomplicated anesthetic induction, maintenance, and recovery. Time to extubation, sternal recumbency, and walking with minimal ataxia was similar for each treatment.

Cardiovascular effects of intravenous bolus administration and infusion of ketamine-midazolam in isoflurane-anesthetized dogs

Summary Cardiovascular effects of iv administered ketamine (10 mg/kg) and midazolam (0.5 mg/kg) were determined in 12 healthy isoflurane-anesthetized (1.7% end-tidal concentration) dogs. Six dogs received a ketamine-midazolam combination (k-m) as a bolus over 30 seconds and 6 dogs received k-m as an infusion over 15 minutes. Ketamine-midazolam combination as a bolus and an infusion caused early significant (P &lt; 0.05) reductions in mean systemic blood pressure, cardiac index, and stroke index, which returned to baseline values near the end of the study. Heart rate decreased significantly (P &lt; 0.05) in dogs of the infusion group and returned to the baseline value near the end of the study. One dog died after k-m bolus administration. Mean maximal decreases from baseline for systemic blood pressure, cardiac index, and stroke index were significantly (P &lt; 0.05) greater in dogs of the bolus group than in dogs of the infusion group; therefore, cardiovascular effects of k-m after infusion were less severe than those after bolus. Base excess and pHa decreased significantly (P &lt; 0.05) in the infusion group, although similar changes occurred in both groups. Four dogs were maintained with 1.7% end-tidal isoflurane to determine temporal effects of isoflurane; these dogs did not receive k-m. Increases in heart rate, cardiac index, stroke index, and left and right ventricular stroke work indexes were significant (P &lt; 0.05) at various sample collection intervals, particularly during the later stages of the study. Isoflurane anesthesia effectively blocked the cardiostimulatory properties of k-m. Ketamine-midazolam combination should be used cautiously during isoflurane anesthesia, and administration by slow infusion may be safer than by rapid bolus administration.

Cardiorespiratory effects of intravenous bolus administration and infusion of ketamine-midazolam in dogs

Summary Twelve healthy dogs were used to determine the cardiorespiratory effects of iv administered ketamine (10 mg/kg of body weight) and midazolam (0.5 mg/kg). Half the dogs received a ketamine-midazolam combination (k-m) as a bolus over 30 seconds and the other half received the k-m as an infusion over 15 minutes. Induction of anesthesia by use of k-m was good in all dogs. Ketamine-midazolam combination as a bolus or infusion induced minimal cardiorespiratory effects, except for significant (P &lt; 0.05) increases in mean heart rate and rate-pressure product. The increase in heart rate was greater in dogs of the infusion group. Mild and transient respiratory depression was observed in dogs of both groups immediately after administration of k-m, but was greater in dogs of the bolus group than in dogs of the infusion group. Duration of action of k-m for chemical restraint was short. Salivation and defecation were observed in a few dogs. Extreme muscular tone developed in 1 dog after k-m bolus administration.