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Randomized double-blind comparison of ketamine-propofol, fentanyl-propofol and propofol-saline on haemodynamics and laryngeal mask airway insertion conditions

Goh PK, Chiu CL, Wang CY, Chan YK, Loo PL

Anaesth Intensive Care, 2005 Apr;33(2):223-8.
PMID: 15960405

The aim of this prospective, double-blind, randomized, placebo-controlled clinical trial was to investigate whether the administration of ketamine before induction with propofol improves its associated haemodynamic profile and laryngeal mask airway (LMA) insertion conditions. Ninety adult patients were randomly allocated to receive either ketamine 0.5 mg x kg(-1) (n = 30), fentanyl 1 microg x kg(-1) (n = 30) or normal saline (n = 30), before induction of anaesthesia with propofol 2.5 mg x kg(-1). Insertion of the LMA was performed 60s after injection of propofol. Arterial blood pressure and heart rate were measured before induction (baseline), immediately after induction, immediately before LMA insertion, immediately after LMA insertion and every minute for three minutes after LMA insertion. Following LMA insertion, the following six subjective endpoints were graded by a blinded anaesthestist using ordinal scales graded 1 to 3: mouth opening, gagging, swallowing, movement, laryngospasm and ease of insertion. Systolic blood pressure was significantly higher following ketamine than either fentanyl (P = 0.010) or saline (P = 0.0001). The median (interquartile range) summed score describing the overall insertion conditions were similar in the ketamine [median 7.0, interquartile range (6.0-8.0)] and fentanyl groups [median 7.0, interquartile range (6.0-8.0)]. Both appeared significantly better than the saline group [median 8.0, interquartile range (6.75-9.25); P = 0.024]. The incidence of prolonged apnoea (> 120s) was higher in the fentanyl group [23.1% (7/30)] compared with the ketamine [6.3% (2/30)] and saline groups [3.3% (1/30)]. We conclude that the addition of ketamine 0.5 mg x kg(-1) improves haemodynamics when compared to fentanyl 1 microg x kg(-1), with less prolonged apnoea, and is associated with better LMA insertion conditions than placebo (saline).

Matched MeSH terms: Ketamine/pharmacology*
Fulltext Chemical immobilization of free-ranging and captive Sunda clouded leopards (Neofelis diardi) with two anesthetic protocols: medetomidine-ketamine and tiletamine-zolazepam

Nájera F, Hearn AJ, Ross J, Ramírez Saldivar DA, Evans MN, Guerrero-Sánchez S, et al.

J Vet Med Sci, 2017 Nov 17;79(11):1892-1898.
PMID: 28904261 DOI: 10.1292/jvms.17-0259

There is currently no available information regarding the veterinary management of Sunda clouded leopards (Neofelis diardi), either in captivity or in the wild. In this study, 12 Sunda clouded leopards were anesthetized between January 2008 and February 2014 for medical exams, and/or GPS-collaring. Seven wild-caught individuals were kept in captivity and 5 free-ranging animals were captured by cage traps. Two anesthesia combinations were used: medetomidine-ketamine (M-K) or tiletamine-zolazepam (T-Z). Atipamezole (0.2 mg/kg im) was used as an antagonist for medetomidine. Medetomidine (range: 0.039-0.054 mg/kg) and ketamine (range: 3-4.39 mg/kg) were administered during 5 immobilizations, resulting in median induction times of 7 min. After a median anesthesia time of 56 min, atipamezole was injected, observing effects of antagonism at a median time of 12 min. T-Z (range: 6.8-10.8 mg/kg) was administered on 7 occasions. Median induction times observed with this combination were shorter than with M-K (4 min vs 7 min; P=0.04), and anesthesia and recovery times were significantly longer (244 and 35 min vs 56 and 16 min, respectively; P=0.02). Lower heart rates were measured in the M-K group, while lower rectal temperatures were found in the T-Z group. Both combinations resulted in safe and reliable immobilizations, although given the favorable anesthesia and recovery times of M-K, we recommend this approach over T-Z for the veterinary handling of Sunda clouded leopards.

Matched MeSH terms: Ketamine/administration & dosage*
Evaluation of anaesthetic and cardiorespiratory effects after intramuscular administration of alfaxalone alone, alfaxalone-ketamine and alfaxalone-butorphanol-medetomidine in common marmosets (Callithrix jacchus)

Miyabe-Nishiwaki T, Miwa M, Konoike N, Kaneko A, Ishigami A, Natsume T, et al.

J Med Primatol, 2020 12;49(6):291-299.
PMID: 32654222 DOI: 10.1111/jmp.12482

BACKGROUND: Anaesthesia is often required in common marmosets undergoing various procedures. The aim of this study was to evaluate anaesthetic and cardiopulmonary effects of alfaxalone, alfaxalone-ketamine and alfaxalone-butorphanol-medetomidine in common marmosets.
METHODS: The following treatments were repeatedly administered to seven female common marmosets: Treatment A, alfaxalone (12 mg kg-1 ) alone; treatment AK, alfaxalone (1 mg animal-1 ) plus ketamine (2.5 mg animal-1 ); treatment AMB, alfaxalone (4 mg kg-1 ), medetomidine (50 µg kg-1 ) plus butorphanol (0.3 mg kg-1 ); and treatment AMB-Ati, AMB with atipamezole at 45 minutes.
RESULTS AND CONCLUSIONS: Marmosets became laterally recumbent and unresponsive for approximately 30 minutes in A and AK and for approximately 60 minutes in AMB. The animals showed rapid recovery following atipamezole injection in AMB-Ati. The decrease in heart rate and SpO2 was significantly greater in AMB compared to A and AK. Oxygen supplementation, anaesthetic monitors and atipamezole should be available especially when AMB is administered.

Matched MeSH terms: Ketamine/administration & dosage*
Fulltext Intravenous ketamine is as effective as midazolam/fentanyl for procedural sedation and analgesia in the emergency department

Jamal SM, Fathil SM, Nidzwani MM, Ismail AK, Yatim FM

Med J Malaysia, 2011 Aug;66(3):231-3.
PMID: 22111446

The study compared the effectiveness of ketamine and midazolam/fentanyl as procedural sedation and analgesia agents for reduction of fractures and dislocated joints. Forty-one adult patients were enrolled by convenience sampling. They were randomized to receive ketamine or midazolam/fentanyl. Depth of sedation, pain score, procedural outcome and memory of the procedure were documented. The ketamine group had deeper sedation, but there was no statistical difference in other variables between the two groups. Three patients in the midazolam/fentanyl group had oxygen desaturation. More adverse effects were associated with ketamine. Intravenous ketamine is as effective as midazolam/fentanyl for procedural sedation.

Matched MeSH terms: Ketamine/therapeutic use*
Ketamine and xylazine combinations for short-term immobilization of wild variable flying foxes (Pteropus hypomelanus)

Sohayati AR, Zaini CM, Hassan L, Epstein J, Siti Suri A, Daszak P, et al.

J. Zoo Wildl. Med., 2008 Dec;39(4):674-6.
PMID: 19110718

Collection of biological samples from pteropid bats requires chemical restraint of the bats to minimize risks to humans and stress to the bat. The effectiveness of an intravenous combination of ketamine and xylazine for short-term restraint of wild-caught variable flying foxes (Pteropus hypomelanus) in a field situation was evaluated. Eight adult male variable flying foxes were injected intravenously with 0.1 ml of ketamine and xylaxine containing 5 mg of ketamine and 1 mg of xylazine. The mean induction time was 80 +/- 20 sec, and mean immobilization time was 26 +/- 10 min. The ketamine-xylazine combination used in this study produced effective short-term immobilization of wild variable flying foxes for the collection of biological samples.

Matched MeSH terms: Ketamine/administration & dosage*
Fulltext Serum concentration of ketamine and antinociceptive effects of ketamine and ketamine-lidocaine infusions in conscious dogs

Kaka U, Saifullah B, Abubakar AA, Goh YM, Fakurazi S, Kaka A, et al.

BMC Vet Res, 2016 Sep 9;12(1):198.
PMID: 27612660

Central sensitization is a potential severe consequence of invasive surgical procedures. It results in postoperative and potentially chronic pain enhancement. It results in postoperative pain enhancement; clinically manifested as hyperalgesia and allodynia. N-methyl-D-aspartate (NMDA) receptor plays a crucial role in the mechanism of central sensitisation. Ketamine is most commonly used NMDA-antagonist in human and veterinary practice. However, the antinociceptive serum concentration of ketamine is not yet properly established in dogs. Six dogs were used in a crossover design, with one week washout period. Treatments consisted of: 1) 0.5 mg/kg ketamine followed by continuous rate infusion (CRI) of 30 μg/kg/min; 2) 0.5 mg/kg ketamine followed by CRI of 30 μg/kg/min and lidocaine (2 mg/kg followed by CRI of 100 μg/kg/min); and 3) 0.5 mg/kg ketamine followed by CRI of 50 μg/kg/min. The infusion was administered up to 120 min. Nociceptive thresholds and ketamine serum concentrations were measured before drug administration, and at 5, 10, 20, 40, 60, 90, 120, 140 and 160 min after the start of infusion.

Matched MeSH terms: Ketamine
Fulltext Substance abuse and the HIV situation in Malaysia

Singh D, Chawarski MC, Schottenfeld R, Vicknasingam B

J Food Drug Anal, 2013 Dec;21(4):S46-S51.
PMID: 25278737 DOI: 10.1016/j.jfda.2013.09.033

Heroin continues to be the main drug used in Malaysia, while amphetamine-type stimulants (ATS) have been recently identified as a growing problem. A cumulative total of 300,241 drug users were detected between 1988 and 2006. It is also estimated that Malaysia has 170,000 injecting drug users. HIV prevalence among drug users in the country ranges from 25% to 45%. Currently, there are approximately 380 general medical practice offices that offer agonist maintenance treatments for approximately 10,000 patients. There are 27,756 active patients in 333 general medical practice offices and government-run methadone maintenance treatment (MMT) centers. The Needle Syringe Exchange Program (NSEP) reached out to 34,244 injection drug users (IDUs) in 2011. In the last 2 years (2011 and 2012) the number of detected drug addicts decreased from 11,194 to 9015. The arrests made by the police related to opiate and cannabis use increased from 41,363 to 63,466 between the years 2008 and 2010, but decreased since 2010. An almost four-fold increase in the number of ATS and ketamine users was detected from 2006 (21,653 users) 2012 (76,812). Between 2004 and 2010, the yearly seizures for heroin ranged between 156 to 270 kg. However, in 2010 and 2011, heroin seizures showed a significant increase of 445kg and 410.02 kg, respectively. There has been a seizure of between 600 to 1000kg of syabu yearly from 2009 to 2012. Similar to heroin, increased seizures for Yaba have also been observed over the last 2 years. A significant increase has also been recorded for the seizures of ecstasy pills from 2011 (47,761 pills) to 2012 (634,573 pills). The cumulative number of reported HIV infections since 1986 is 94,841. In 2011, sexual activity superseded injection drug use as the main transmission factor for the epidemic. HIV in the country mainly involves males, as they constitute 90% of cumulative HIV cases and a majority of those individuals are IDUs. However, HIV infection trends are shifting from males to females. There are 37,306 people living with HIV (PLHIV) who are eligible for treatment, and 14,002 PLHIV were receiving antiretroviral treatment (ART) in 2011. The decreasing trend of heroin users who have been detected and arrested could be due to the introduction of medical treatments and harm reduction approaches for drug users, resulting in fewer drug users being arrested. However, we are unable to say with certainty why there has been an increase in heroin seizures in the country. There has been an increasing trend in both ATS users and seizures. A new trend of co-occurring opiate dependence and ATS underscores the need to develop and implement effective treatments for ATS, co-occurring opiate and ATS, and polysubstance abuse disorders. The low numbers of NSEP clients being tested for HIV underscores our caution in interpreting the decline of HIV infections among drug users and the importance of focusing on providing education, prevention, treatment, and outreach to those who are not in treatment.

Matched MeSH terms: Ketamine
Fulltext Profound swim stress-induced analgesia with ketamine

Ahmad AH, Ismail Z, Than M, Ahmad A

Malays J Med Sci, 2008 Jan;15(1):13-22.
PMID: 22589610 MyJurnal

The potential of ketamine, an N-methyl D-aspartate (NMDA) receptor antagonist, in preventing central sensitization has led to numerous studies. Ketamine is increasingly used in the clinical setting to provide analgesia and prevent the development of central sensitization at subanaesthetic doses. However, few studies have looked into the potential of ketamine in combination with stress-induced analgesia. This study looks at the effects of swim stress, which is mediated by opioid receptor, on ketamine analgesia using formalin test. Morphine is used as the standard analgesic for comparison. Adult male Sprague-Dawley rats were assigned to 6 groups: 3 groups (stressed groups) were given saline 1ml/kg intraperitoneally (ip), morphine 10mg/kg ip or ketamine 5mg/kg ip and subjected to swim stress; 3 more groups (non-stressed groups) were given the same drugs without swim stress. Formalin test, which involved formalin injection as the pain stimulus and the pain score recorded over time, was performed on all rats ten minutes after cessation of swimming or 30 minutes after injection of drugs. Combination of swim stress and ketamine resulted in complete analgesia in the formalin test which was significantly different from ketamine alone (p<0.05) and saline with stress (p<0.01). There is no significant difference between ketamine stressed and morphine stressed. These results indicate that ketamine and swim stress act synergistically to produce profound analgesia in the formalin test. This suggests that in the clinical setting, under stressful situations such as operative stress, ketamine is capable of producing profound analgesia at a subanaesthetic dose.

Matched MeSH terms: Ketamine
Dexmedetomidine and ketamine sedation for dental extraction in children with cyanotic heart disease

Hasan MS, Chan L

J Oral Maxillofac Surg, 2014 Oct;72(10):1920.e1-4.
PMID: 24985961 DOI: 10.1016/j.joms.2014.03.032

Treating children with cyanotic congenital heart disease poses many challenges to anesthesiologists because of the multiple problems associated with the condition. The anesthetic technique and drugs used perioperatively can affect a patient's physiologic status during surgery. The adherence to certain hemodynamic objectives and the avoidance of factors that could worsen the abnormal cardiopulmonary physiology cannot be overemphasized. In the present case series, we describe the use of a dexmedetomidine-ketamine combination for dental extraction in spontaneously breathing children with cyanotic congenital heart disease. The anesthetic concerns regarding airway management, the pharmacologic effects of drugs, and maintenance of adequate hemodynamic, blood gases, and acid-base status are discussed.

Matched MeSH terms: Ketamine/administration & dosage*
Fulltext Intact urothelial barrier function in a mouse model of ketamine-induced voiding dysfunction

Rajandram R, Ong TA, Razack AH, MacIver B, Zeidel M, Yu W

Am J Physiol Renal Physiol, 2016 05 01;310(9):F885-94.
PMID: 26911853 DOI: 10.1152/ajprenal.00483.2015

Ketamine is a popular choice for young drug abusers. Ketamine abuse causes lower urinary tract symptoms, with the underlying pathophysiology poorly understood. Disruption of urothelial barrier function has been hypothesized to be a major mechanism for ketamine cystitis, yet the direct evidence of impaired urothelial barrier function is still lacking. To address this question, 8-wk-old female C57BL/6J mice were injected intraperitoneally with 30 mg·kg(-1)·day(-1) ketamine for 12 wk to induce ketamine cystitis. A spontaneous voiding spot assay showed that ketamine-treated mice had increased primary voiding spot numbers and smaller primary voiding spot sizes than control mice (P < 0.05), indicating a contracted bladder and bladder overactivity. Consistently, significantly increased voiding frequency was observed in ketamine-treated mice on cystometrograms. These functional experiments indicate that ketamine induces voiding dysfunction in mice. Surprisingly, urothelial permeability in ketamine-treated mice was not changed when measured using an Ussing chamber system with isotopic urea and water. Mouse urothelial structure was also not altered, and intact umbrella cell structure was observed by both transmission and scanning electron microscopy. Furthermore, immunostaining and confocal microscopy confirmed the presence of a well-defined distribution of zonula occuldens-1 in tight junctions and uroplakin in umbrella cells. In conclusion, these data indicate that ketamine injection induces voiding dysfunction in mice but does not necessarily disrupt mouse bladder barrier function. Disruption of urothelial barrier function may not be the major mechanism in ketamine cystitis.

Matched MeSH terms: Ketamine