The influence of neonatal ketamine injection on pain sensitivity and audiogenic seizures in adult rats

The remote effects of neonatal (on the 3d-to-9th postnatal days) ketamine injections (10 and 50 mg/kg in 20 microliters of distilled water, s.c.) were analyzed in adult Wistar, WAG/Rij, and KM (a strain with high audiogenic sensitivity) rats. Both ketamine and water injections increased pain sensitivity in adult rats. Neonatally injected water increased the mean score of seizures in Wistar and WAG/Rij, whereas ketamine water solution injected in the dose of 50 mg/kg did not change the seizure intensity (as compared to the intact control). Consequently, ketamine significantly reduced the mean score of the audiogenic seizure fit without change in its latency. In highly sensitive KM rats the neonatally injected ketamine (50 mg/kg) significantly shortened the mean latency of the fit onset, and fit stages developed faster. Thus, the neonatal ketamine injection increased the audiogenic seizure susceptibility of brain structures in KM rats.     

Effects of serial anesthesia using ketamine or ketamine/medetomidine on hematology and serum biochemistry values in rhesus macaques (Macaca Mulatta)

Background  This study aimed at determining the cumulative effect of daily anesthesia, using two drug regimens, over hematological and biochemical parameters.
Methods  Blood samples were obtained from rhesus monkeys 20 minutes after intramuscular administration of ketamine or ketamine/medetomidine combination for three consecutive days and results were evaluated to determine their effect on hematological and serum biochemistry values. Statistical significance of drug, day, and interaction of these two variables were evaluated.
Results  Drug effect resulted in a dramatic increase of aspartate aminotransferase and creatine kinase values. Day effect resulted in decreases of RBC, HCT, Hgb, and alkaline phosphatase but an increase of other biochemical parameters evaluated. The drug/day interaction effect was found to be –significant for RBC, platelets, aspartate aminotransferase, alanine aminotransferase, and creatine kinase values.
Conclusion  The results of our study suggest a cumulative effect of serial anesthesia and should be an important consideration when interpreting hematology and serum biochemistry in rhesus macaques.     

Influence of restraint and ketamine anesthesia on adrenal steroids, progesterone, and gonadotropins in rhesus monkeys

Changes in gonadotropins, progesterone, cortisol, DHA, and DHAS were monitored in 10 female rhesus monkeys (Days 20-23 of the menstrual cycle) subjected to cage restraint with or without ketamine anesthesia for successive venipunctures. All animals were bled without sedation for 2 hr at 30-min intervals. Then 4 of the animals were anesthetized with ketamine-HCl and bleedings in all animals were continued for an additional 2.5 hr. FSH and progesterone were not appreciably affected by either restraint technique. LH declined steadily for the duration of the bleedings (P less than 0.05). Serum levels of cortisol and the adrenal androgens increased twofold (P less than 0.05). Anesthesia with ketamine had no effect on any of the six variables when compared with saline controls. Cortisol and dehydroepiandrosterone (DHA) levels tended to plateau (P less than 0.01) after 2 hr in both treated and control groups. In contrast, dehydroepiandrosterone sulfate (DHAS) levels increased continuously throughout the entire study period. These data indicate that ketamine anesthesia does not alter endocrine responses to venipuncture when administered following cage restraint of conscious animals. These findings further confirm the difficulties in obtaining estimates of basal levels of hormones which are responsive to stress and suggest that the first sample may provide the best estimate.     

Guaiphenesin-ketamine-xylazine infusion to maintain anesthesia in mules undergoing field castration

Background

In order to determine whether a combination of guaiphenesin, ketamine and xylazine can induce safe and satisfactory anaesthesia in mules undergoing field castration, eight healthy adult intact male mules were employed. They were premedicated with intravenous (IV) xylazine (1.3 mg/kg); an additional dose of xylazine (0.3 mg/kg IV) was administered in case of inadequate depth of sedation. Anaesthesia was induced with IV thiopental (6 mg/kg). The quality of sedation and induction was recorded. Anaesthesia was maintained with an infusion of guaiphenesin (50 mg/mL), ketamine (2 mg/mL) and xylazine (1 mg/mL) (GKX). The spermatic cord of each testis was infiltrated with 5 mL of 2% lidocaine. During anaesthesia heart rate (HR), respiratory rate (RR), rectal temperature (RT) and haemoglobin oxygen saturation (SpO₂) were measured every 5 min. The data were analysed with simple one-way analysis of variance (ANOVA). A P value < 0.05 was considered statistically significant. Time of anesthesia, time of surgery and time of recovery were recorded.

Results

Only one mule required an additional dose of xylazine to achieve a satisfactory depth of sedation. Thiopental at the dose of 6 mg/kg IV resulted in smooth induction and lateral recumbency in all animals. GKX provided adequate anaesthesia to perform castration in all mules. Muscle relaxation was deemed adequate and physiological variables remained stable and within references values during the anaesthesia and did not change in response to surgical stimulation. Time (mean ± standard deviation) from the end of the infusion to sternal recumbency and time from sternal recumbency to standing were 27.7 ± 4.6 and 30.1 ± 7.7 min, respectively.

Conclusions

The combination of xylazine, thiopental and GKX provides satisfactory short-term anaesthesia in mules undergoing field castration.

     

Effect of ketamine anesthesia on daily food intake in Macaca mulatta and Cercopithecus aethiops

Ketamine hydrochloride is frequently administered to non-human primates as a means of chemical restraint. This procedure can be a frequent source of stress to monkeys at research facilities, impacting animal health, well-being and research quality. This study was designed to measure ketamine's effect on daily food intake, a parameter that reflects and influences animal well-being and directly impacts research studies. On five occasions, baseline daily food intake was compared to daily food intake occurring 24, 48, 72, 96, and 120 h after an intramuscular injection of 10 mg/kg ketamine in male African green monkeys (AGMs) (Cercopithecus aethiops) and male and female rhesus macaques (Macaca mulatta). AGMs and female rhesus macaques had significantly reduced daily food intake during the first 4 days after receiving ketamine. The AGMs continued to display significantly reduced daily food intake on the fifth day after ketamine. The male rhesus macagues showed a trend toward reduced daily food intake, greatest during the first 2 days and remaining less than baseline intake through the fifth day following ketamine. The degree of observed food intake reduction was most severe at the 24 h (mean percent intake reduction: AGMs: 57%; rhesus males: 48%; rhesus females: 40%) and 48 h time points (AGMs: 24%; rhesus males: 14%; rhesus females: 13%). A subset of the AGMs that did not receive ketamine, but observed other animals in the room receive ketamine, showed reduced food intake at 24 and 48 h after ketamine, though not to the degree associated with ketamine administration. These results indicate that ketamine anesthesia is associated with a prolonged reduction in daily food intake in AGMs and rhesus macaques. Frequent use of ketamine in non-human primates may have a significant impact on animal health and well-being, and alternatives to its use warrant consideration.     

Long term anesthesia using a continuous infusion of guaifenesin, ketamine and xylazine in cats.

Cats (Felis catus) were anesthetized with a solution containing guaifenesin, ketamine and xylazine (GKX) in 0.9% saline. Anesthesia was induced by intravenous (IV) injection and was maintained for 6 hours by IV infusion. Heart rate, respiratory rate and PvO2 did not change significantly during the 6 hour monitoring period and remained consistently within the published normal ranges for cats. Although the PvCO2 did not change significantly, many values were abnormal. Venous pH decreased to slightly below normal values. Lead II ECG tracings showed no abnormalities. Loss of response to pedal pinch and jaw tone indicates maintenance of a surgical plane of anesthesia and adequate muscle relaxation throughout the 6 hour anesthetic period. Cats exhibited voluntary motor movement and were in sternal recumbency in just over 2 hours and were showing no residual clinical effects of the anesthesia 16 hours later. Although a transient mild acidosis was observed, we conclude that GKX provides a safe, effective and easily administered anesthetic regime for cats for periods up to 6 hours.     

Treatment-time-dependent difference of ketamine pharmacological response and toxicity in rats

Circadian rhythms impact many physiological functions that may affect drug pharmacological response. Ketamine is a dissociative agent commonly used for surgical anesthesia in rats. The aim of the present study was to analyze the central nervous system (CNS) depression and lethality of ketamine injected intraperitoneally at different times during the 24 h. The study was conducted in October 2001, spring in the Southern hemisphere. Female prepuberal Sprague-Dawley rats synchronized to a 12h light:12h dark cycle (light, 07:00h-19:00h) were studied. Ketamine (40 mg/kg) was administered to one of six different clock-time treatment groups (n=6-7 rats each). Duration of latency period, ataxia, loss of righting reflex (LRR), post-LRR ataxia, and total pharmacological response were determined by visual assessment. To investigate acute toxicity, ketamine lethal dose 50 (148.0 mg/kg) was also administered as a single injection to six different treatment-time groups of rats. Significant temporal differences and circadian rhythms were detected in drug-induced post-LRR ataxia and total pharmacological response duration. The longest pharmacological response occurred in rats injected during the light (rest) phase and the shortest response in the dark (activity) phase. No circadian rhythm was detected in acute toxicity. The study findings indicate that the duration of CNS depression of ketamine in rats exhibits circadian rhythmic variation.     

Dissociative anesthesia for safety's sake: ketamine and diazepam--a 35-year personal experience

Recent discussions and proposed rules and regulations regarding outpatient surgery facilities have raised the question of the appropriateness of general anesthesia versus heavy sedation. The controversy is based mostly on anecdotal information and the prejudice of the authors. A recent article that describes the improved platelet function induced by ketamine adds patient safety to the rationale for sedation. Most of us have trained in university settings where an entire department was devoted to general anesthesia and little true outpatient surgery was performed. When ambulatory facilities were available, they were usually staffed by anesthesiologists. Indeed, the first free-standing outpatient surgery center in Phoenix, Arizona, was owned and operated by a local group of anesthesiologists. Properly administered, diazepam and ketamine dissociative sedation is safe and effective for every aesthetic procedure, regardless of size or duration, and it should be available for all aesthetic surgeons. In the author's experience, more than 30,000 procedures have been performed with this method since 1966 without a single case of deep vein thrombosis or pulmonary embolus. In contrast, a former associate, because of his lack of experience, chose to use general anesthesia for a few larger cases in another facility. One of those cases, an abdominoplasty, resulted in a serious case of deep vein thrombosis with subsequent alleged disability and litigation. Therefore, the author is writing to share his extensive experience with his colleagues in hopes that these safe systems will become more widespread and to spare future patients the attendant unnecessary increased morbidity and mortality associated with general anesthesia.     

Hematological and serum biochemical values in cynomolgus monkeys anesthetized with ketamine hydrochloride

The effects of ketamine anesthesia on both hematological and serum biochemical variables were investigated in 19 male and 15 female cynomolgus monkeys. Blood samples were obtained from the cephalic vein within 30 minutes of an intramuscular injection of ketamine hydrochloride (10 mg/kg). Ketamine anesthesia caused a reduction in leukocyte counts and a significant reduction in lymphocytes percentages. Ketamine anesthesia also increased the serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine phosphokinase (CPK), but reduced the serum concentrations of glucose, inorganic phosphate, sodium and potassium. The alterations of hematological and serum biochemical values will be discussed. These alterations should be considered when designing studies for and interpreting data from cynomolgus monkeys.     

A comparison of ketamine/xylazine and ketamine/xylazine/acepromazine anesthesia in the rabbit

Parenteral anesthetic combinations such as ketamine and xylazine have become the agents of choice for anesthesia in the rabbit, because they are effective, easily administered and inexpensive. A number of recent reports have recommended including acepromazine in this combination, but a critical evaluation of this combination in the rabbit has not been reported. Five adult New Zealand white rabbits were anesthetized intramuscularly with ketamine (35 mg/kg) and xylazine (5 mg/kg) with or without acepromazine (0.75 mg/kg). The study was conducted in a double blind fashion, where each rabbit was administered both combinations at a minimum of 7 day intervals. Physiologic parameters were evaluated including heart rate, respiratory rate, central arterial blood pressure, pedal, palpebral and postural reflex activity. The duration of general anesthesia, estimated by the time elapsed between the loss and return of the palpebral reflex, was greater (means = 99 +/- 20 minutes) when acepromazine was employed in the combination compared to (means = 77 +/- 5 minutes) when ketamine/xylazine were used alone. Mean central arterial blood pressure reached a lower level when acepromazine was utilized (means = 46 +/- 8 mm/Hg) than when it was not (means = 57 +/- 12 mm/Hg.). The addition of acepromazine in a ketamine/xylazine combination resulted in a 28% longer period of anesthesia, a 19% lower mean central arterial blood pressure and a 32% longer recovery of postural reflexes. The ketamine/xylazine/acepromazine combination is a useful regimen for normovolemic animals when anesthetic duration greater than that produced by ketamine/xylazine alone is required.     

Effect of butorphanol,midazolam or ketamine on romifidine based sedation in horses during standing cheek tooth removal

Background

Standing surgery, especially dental procedures, are commonly performed in horses. This leads to an increasing demand for reliable sedation protocols. Therefore, it was the purpose of this study to investigate the influence of butorphanol, midazolam or ketamine on romifidine based sedation in horses during cheek tooth removal.

Methods

Forty horses presented for tooth extraction were divided in four groups using matched pair randomization. Group R was sedated with romifidine (bolus 0.03 mg/kg, followed by a constant rate infusion (CRI) 0.05 mg/kg/h) and group RB with romifidine (same dose) and butorphanol (0.02 mg/kg; CRI 0.04 mg/kg/h). Group RM received romifidine (same dose) and midazolam (0.02 mg/kg; CRI 0.06 mg/kg/h) whereas group RK was administered romifidine (same dose) and ketamine (0.5 mg/kg; CRI 1.2 mg/kg/h). If sedation was not adequate a top up bolus of romifidine (0.01 mg/kg) was administered. The quality of sedation and the conditions for tooth extraction, the level of ataxia, chewing, head and tongue movement were evaluated by using a scoring system. The investigator was blinded to the applied sedation protocol. Furthermore, serum cortisol concentrations before, during and after the procedure were analyzed to gain more information about the stress level of the horses.

Results

Horses in group RM showed significantly less chewing and tongue activity compared to horses sedated with romifidine alone or with butorphanol additionally, but also significantly higher levels of ataxia. The quality of sedation was significantly better if romifidine was administered in combination with ketamine compared to romifidine alone. Furthermore, horses of group RK needed less additional romifidine boli compared to all other groups. Blood cortisol concentrations during surgery in groups RB and RM remained unchanged. Horses of group R showed higher cortisol concentrations during sedation compared to horses of groups RB and RM.

Conclusion

Romifidine alone at an initial bolus dose of 0.03 mg/kg followed by a constant rate infusion of 0.05 mg/kg/h was insufficient to obtain an adequate level of sedation and led to increased stress levels, whereas the addition of butorphanol inhibited the stress response. The combination of romifidine with either midazolam or ketamine improved sedation quality and surgical conditions.

     

The effect of the novel partial alpha2-adrenoceptor agonist naphthylmedetomidine on the basic cardiorespiratory parameters and behavior in rhesus monkeys

Background  The aim of this study was to compare cardiorespiratory and behavioral profile of a new alpha 2-adrenoceptor ligand naphthylmedetomidine with medetomidine in rhesus monkeys.
Methods  Naphthylmedetomidine or medetomidine (50 μg/kg) together with ketamine (3 mg/kg) and hyaluronidase (150 IU/kg) i.m was administered to 35 rhesus monkeys. Behavioral changes were then observed together with blood pressure, heart rate and oxygen saturation of hemoglobin.
Results  The onset of sedation, ataxia, and reduction of aggression was similar in both treatment groups. Immobilization was observed only in medetomidine treated animals, while in naphthylmedetomidine treated animals loss of aggressiveness was observed but the animals never completely lost mobility. Naphthylmedetomidine showed less prominent effects on cardiorespiratory functions compared with medetomidine.
Conclusions  Our results suggest that naphthylmedetomidine can be used to induce sedation in primates and other small animals while avoiding the serious side effects observed after administration of the currently used full α₂-AR agonists.     

Butorphanol/xylazine/ketamine immobilization of free-ranging Baird's tapirs in Costa Rica

Cardiopulmonary effects and the utility of a butorphanol/xylazine/ketamine combination were evaluated during twenty immobilizations of sixteen Baird's tapirs (Tapirus bairdii) between March 1996 and January of 1998 in Corcovado National Park (Costa Rica). The animals were attracted to a bait site and darted from tree platforms. The tapirs were estimated to weigh between 200 to 300 kg. Actual weights of three tapirs taken at later dates fell within the estimated range. A butorphanol, 48+/-1.84 (x +/- SE) mg/animal IM, and xylazine, 101+/-2.72 mg/animal IM, combination was used to immobilize the animals. In some instances, ketamine was used either IM or IV at 187+/-40.86 mg/animal to prolong the immobilization period in addition to the butorphanol/xylazine combination. Naltrexone was used IM to reverse butorphanol at 257+/-16.19 mg/animal. Either yohimbine, 34+/-0.61 or tolazoline at 12+/-10.27 mg/animal, was used to reverse xylazine. The mean time from dart impact to first visible effect was 4.63+/-0.50 min (x +/- SE). Mean time to sternal recumbency was 12.21+/-1.08 min. Mean time the tapirs were immobilized was 45.63+/-3.6 min. Mean time to return to sternal recumbency and standing in animals that received yohimbine and naltrexone was 3.16+/-1.06 and 5.33+/-1.45 min, respectively. Mean time to return to sternal recumbency and standing in animals that received tolazoline and naltrexone was 1.57+/-0.39 and 3.14+/-0.51 min, respectively. Cardiopulmonary parameters including heart rate, respiratory rate, body temperature, electrocardiogram, percent oxygen satoration, and indirect blood pressure were recorded. Arterial blood gas analysis was performed on four animals. A mild degree of hypoxemia was evidenced by low arterial oxygen saturations. Five of 14 (36%) animals measured had oxygen saturations below 90%. Bradycardia (heart rates <45 BPM) was an expected finding in 11 (55%) immobilizations. Induction, recovery and muscle relaxation of each immobilization was graded. Premature arousal, which occurred in six (30%) animals, was the only problem associated with the immobilizations. Butorphanol/xylazine is a recommended protocol for immobilization of calm, free-ranging tapirs lasting less than 30 min. Supplemental intravenous administration of ketamine is recommended for longer procedures. Nasal insufflation of oxygen is recommended.     

The efficacy of orally dosed ketamine and ketamine/medetomidine compared with intramuscular ketamine in rhesus macaques (Macaca mulatta) and the effects of dosing route on haematological stress markers

BACKGROUND: This study compared the efficacy of two orally-dosed (PO) anaesthetic regimens for chemical immobilization in rhesus macaques (Macaca mulatta), versus the standard protocol of intramuscular (TM) ketamine. In addition, the effects of dosing route on haematological stress markers were evaluated. METHODS: Testing was conducted on 18 chronically housed animals. Animals were trained to accept oral dosing and then randomly assigned to one of three drug regimens: (1) ketamine IM, (2) ketamine PO, (3) Ketamine/medetomidine PO. Sedation levels for each regimen were evaluated. RESULTS: Oral dosing alone was not sufficient to achieve a plane of sedation that allowed for safe handling. Serum cortisol and glucose levels were unchanged across groups, although differences were observed in the leukogram profiles. CONCLUSION: The oral dosages used in this study fell short in providing adequate sedation for safe handling for routine veterinary procedures. Leukogram profiles indicated that orally dosed animals experienced a higher level of stress.     

Effects of yohimbine on bradycardia and duration of recumbency in ketamine/xylazine anesthetized ferrets

Eleven adult ferrets (Mustela putorius furo) were anesthetized with ketamine hydrochloride (25 mg/kg, IM) and xylazine hydrochloride (2 mg/kg, IM). Fifteen minutes post-ketamine/xylazine injection, ferrets were treated with yohimbine hydrochloride at a dose of 0.5 mg/kg, or an equal volume of physiologic saline, intramuscularly. Each ferret served as its own control by randomly receiving both treatments with a minimum interval of 2 weeks between treatments on any one ferret. At 15 minutes post-ketamine/xylazine injection, mean heart rate measurements for both treatment groups were 27% less than the mean heart rate measurement reported for unanesthetized ferrets. Intramuscular administration of yohimbine antagonized the ketamine/xylazine induced bradycardia in 10 of the 11 ferrets, (p = 0.0001). In yohimbine treated ferrets, an increase in mean heart rate measurement was noted 5 minutes after the intramuscular administration of yohimbine, and followed, over the next 15 minutes, by a progressive increase in mean heart rate. However, a corresponding decrease in mean heart rate measurement was observed in saline treated controls. Fifteen minutes after the injection of yohimbine, the mean heart rate measurement of yohimbine treated animals had increased to 194 beats per minute. This mean heart rate measurement is nearly 30% greater than the mean heart rate of 150 beats per minute measured at 15 minutes post-saline injection in saline treated controls. Also, yohimbine treatment significantly reduced duration of recumbency in 10 of 11 ferrets (p = 0.0001). Mean duration of recumbency for yohimbine treated ferrets was 41 +/- 9.7 minutes, whereas mean duration of recumbency for saline treated ferrets was determined to be 80 +/- 11.4 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma-free amino acid concentrations during ketamine anesthesia in the rhesus monkey: a short methodological study

The effect of ketamine anesthesia on the pattern of free amino acids in plasma was investigated in four healthy non-pregnant rhesus monkeys. Blood samples were collected at intervals during a period of 150 min both with and without anesthesia. Repeated measures analysis of variance, with time and ketamine/control as trial factors, was used. In only four amino acids were any changes with time or with ketamine treatment observed, the rest remaining unchanged. Ketamine anesthesia seemed to reduce the concentrations of several amino acids, but the findings were not conclusive.     

The effects of ketamine anesthesia on hematological and serum biochemical values in female cynomolgus monkeys (Macaca fascicularis)

The effects of ketamine anesthesia (15 mg/kg body weight) on hematological and serum biochemical values were examined in six female cynomolgus monkeys (Macaca fascicularis) who were born in the wild. As control, another six female cynomolgus monkeys of the same origin were injected with physiological saline. The white blood cell count, total protein concentration, albumin concentration and calcium concentration decreased after the injection of ketamine, whereas the red blood cell count, hematocrit value, hemoglobin concentration, total cholesterol concentration, free cholesterol concentration, triglyceride concentration, transaminase activities (GOT, GPT) and alkaline phosphatase activity were not affected. A transient increase of the serum glucose level was observed within 10 minutes after ketamine injection. The relationship between these effects of ketamine anesthesia and serum cortisol levels measured by radioimmunoassay was discussed.     

Immobilization of California sea lions using medetomidine plus ketamine with and without isoflurane and reversal with atipamezole

The use of medetomidine and ketamine, alone and in combination with isoflurane, with atipamezole reversal was evaluated for immobilizing 51 California sea lions (Zalophus californianus) for a variety of medical procedures at a rehabilitation center in northern California (USA) between May 1997 and August 1998. Animals were given 140 microg/kg medetomidine with 2.5 mg/kg ketamine intramuscularly. Mean (+/-SD) time to maximal effect was 8+/-5 min. At the end of the procedure, animals were given 200 microg/kg atipamezole intramuscularly. Immobilization and recovery times were, respectively, 25+/-12 and 9+/-7 min for 35 animals maintained with medetomidine and ketamine alone and 58+/-30 and 9+/-9 min for 16 animals intubated and maintained with isoflurane. No mortalities occurred as a result of the immobilizations. Disadvantages of the medetomidine and ketamine combination included a moderate variation in time to maximal effect and plane of sedation, a large injection volume and high cost. However, this combination offers safe and reversible immobilization that can be easily administered by the intramuscular route and that produces a plane of anesthesia that is sufficient to carry out most routine diagnostic procedures.     

Repeated administration of low dose ketamine for the treatment of monoarthritic pain in the rat

The aim of the present study was to observe the effect of repeated subcutaneous (sc) injections of low doses of ketamine for the treatment of acute inflammatory pain in a complete Freund's adjuvant-induced monoarthritic pain model in rats. The results show: (1) sc injection of ketamine at a dose of 2 mg x kg(-1) or 10 mg x kg(-1) produced significant analgesia (P<0.01) in arthritic rats starting from the 2nd week and 3rd week, respectively. (2) Repeated administration of ketamine produced a significant reduction of the circumference of the arthritic ankle (P<0.05 and P<0.01 with different doses). (3) The body weight of the rats was not affected by continuous administration of ketamine for 4 weeks. No abnormal locomotor behavior was observed (It was concerned but not systemically evaluated in this study). The results suggest that repeated sc injection of ketamine for 4 weeks significantly reduce inflammatory pain in monoarthritis without notable aversive side effects.     

Pediatric premedication: a double-blind randomized trial of dexmedetomidine or ketamine alone versus a combination of dexmedetomidine and ketamine

Background

Preoperative anxiety is common in pediatric patients. When dexmedetomidine is used alone for sedation as premedication, children tend to awaken when separated from their parents, and body movements occur during invasive procedures. We tested the hypothesis that the combination of dexmedetomidine and ketamine may be a useful premedication to alleviate preoperative anxiety and improve cooperation during intravenous cannulation in pediatric patients, while producing minimal adverse events.

Methods

A total of 135 children, aged 2–5 years and American Society of Anesthesiologists status I–II, scheduled for eye surgery were randomly allocated to receive intranasal dexmedetomidine 2.5 μg/kg (group D), oral ketamine 3 mg/kg and intranasal dexmedetomidine 2 μg/kg (group DK), or oral ketamine 6 mg/kg (group K) 30 min before surgery. Sedation state was evaluated every 10 min after premedication and emotional state was assessed during separation from their parents and peripheral intravenous cannulation. Adverse events were recorded for 24 h postoperatively. The primary endpoint was the rate of successful intravenous cannulation.

Results

The rate of successful venous cannulation was 47% with dexmedetomidine alone, 68% with ketamine alone, and 80% with combined premedication (P?=?0.006). The rate of satisfactory separation from parents was not different among groups. The incidence of adverse events was higher in group K compared with the other two groups (postoperative vomiting, P?=?0.0041; respiratory-related complications during the perioperative period, P?=?0.0032; and postoperative psychological/psychiatric adverse events, P?=?0.0152).

Conclusion

The combination of intranasal dexmedetomidine 2 μg/kg and oral ketamine 3 mg/kg produces satisfactory separation from parents and more successful venous cannulation, allowing children to smoothly accept induction of general anesthesia.

Trial registration

Chinese Clinical Trial Register (Unique identifier: ChiCTR-TRC-14004475, Date of registration: 2 April 2014).