ACA App
Annals of Cardiac Anaesthesia Annals of Cardiac Anaesthesia Annals of Cardiac Anaesthesia
Home | About us | Editorial Board | Search | Ahead of print | Current Issue | Archives | Submission | Subscribe | Advertise | Contact | Login 
Users online: 1080 Small font size Default font size Increase font size Print this article Email this article Bookmark this page
 


 

 
     
    Advanced search
 

 
 
     
  
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  


    Abstract
   Introduction
   Literature review
   Summary
   Brief History
    References
    Article Tables

 Article Access Statistics
    Viewed10243    
    Printed196    
    Emailed19    
    PDF Downloaded838    
    Comments [Add]    
    Cited by others 1    

Recommend this journal

 


 
Table of Contents
REVIEW ARTICLE  
Year : 2015  |  Volume : 18  |  Issue : 2  |  Page : 202-209
Ketamine in adult cardiac surgery and the cardiac surgery Intensive Care Unit: An evidence-based clinical review


1 Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland, USA
2 Department of Pharmacy, Emory University School of Medicine, Atlanta, Georgia, USA

Click here for correspondence address and email

Date of Submission07-Apr-2014
Date of Acceptance20-Jan-2015
Date of Web Publication2-Apr-2015
 

   Abstract 

Ketamine is a unique anesthetic drug that provides analgesia, hypnosis, and amnesia with minimal respiratory and cardiovascular depression. Because of its sympathomimetic properties it would seem to be an excellent choice for patients with depressed ventricular function in cardiac surgery. However, its use has not gained widespread acceptance in adult cardiac surgery patients, perhaps due to its perceived negative psychotropic effects. Despite this limitation, it is receiving renewed interest in the United States as a sedative and analgesic drug for critically ill-patients. In this manuscript, the authors provide an evidence-based clinical review of ketamine use in cardiac surgery patients for intensive care physicians, cardio-thoracic anesthesiologists, and cardio-thoracic surgeons. All MEDLINE indexed clinical trials performed during the last 20 years in adult cardiac surgery patients were included in the review.

Keywords: Cardiac surgery; dissociative anesthesia; intensive care; ketamine

How to cite this article:
Mazzeffi M, Johnson K, Paciullo C. Ketamine in adult cardiac surgery and the cardiac surgery Intensive Care Unit: An evidence-based clinical review. Ann Card Anaesth 2015;18:202-9

How to cite this URL:
Mazzeffi M, Johnson K, Paciullo C. Ketamine in adult cardiac surgery and the cardiac surgery Intensive Care Unit: An evidence-based clinical review. Ann Card Anaesth [serial online] 2015 [cited 2021 Jun 21];18:202-9. Available from: https://www.annals.in/text.asp?2015/18/2/202/154478



   Introduction Top


Ketamine is a unique anesthetic drug that provides profound analgesia, hypnosis, and amnesia. It also causes less respiratory depression than other intravenous anesthetics at clinically relevant doses and has sympathomimetic properties that make it a useful drug for patients with impaired cardiac function (e.g.,: Cardiac tamponade or systolic heart failure). Ketamine also has anti-inflammatory properties that are potentially useful in attenuating the inflammatory response to cardiopulmonary bypass (CPB). [1],[2] To date, there has been no concise review of ketamine use in adult cardiac surgery and the cardiac surgery Intensive Care Unit (ICU). For this reason, we provide an evidence-based clinical review of the current literature for cardiac surgeons, cardio-thoracic anesthesiologists, and intensive care providers.


   Literature review Top


To identify relevant articles for the review we conducted a systematic review of MEDLINE with the following phrases: "Ketamine and cardiac surgery," "ketamine and coronary artery bypass," "ketamine and valve surgery," "ketamine and aortic surgery," "ketamine and heart transplant," "ketamine and cardiac ICU," and "ketamine and ICU." The authors also identified studies of interest from the reference lists in articles that were reviewed. All authors agreed upon which studies to include in the review. Only studies that were performed during the last 20 years were included in the list of clinical studies.


   Brief History Top


In 1962 Calvin Stevens Ph.D., an organic chemistry professor at Wayne State University (Detroit, Michigan, USA), synthesized a number of phencyclidine derivates for Parke Davis Pharmaceuticals. [3] Parke Davis had been investigating phencyclidine as a human anesthetic agent but found that it lead to the unpleasant side effect of prolonged emergence delirium. For this reason, they hoped to identify a short-acting chemical derivative that would limit these adverse effects. The derivative compounds were tested in nonhuman primates and one compound, CI-581, appeared to be short-acting and provide excellent anesthesia. This compound was selected for human trials and later became known as "ketamine."

Ketamine was first tested in humans at the Parke Davis Research Unit of Jackson Prison in Michigan. The first human received the drug on August 3, 1964 and in 1965 Domino et al. published their initial data from human subjects coining the term "dissociative anesthesia." [4] Further studies of the drug in human subjects continued throughout the 1960s. By 1970, it was approved as an anesthetic agent by the United States Food and Drug Administration.

Pharmacology

Ketamine's basic chemical structure is a chlorophenyl group attached to a modified cyclohexanone ring. The cyclohexanone ring contains a chiral carbon at the C-2 position and thus there are two enantiomers (S + or R ). Most commercial preparations contain a racemic mixture. The S + and R enantiomers have similar pharmacodynamic properties, but the S + enantiomer is more potent.

Ketamine is readily soluble in water and has a pKa of 7.5. Parenteral preparations are commercially available, and oral preparations can be compounded; however, only a small amount of an oral dose is absorbed due to extensive first pass metabolism. [5] When injected intravenously its effects are rapid, occurring in approximately 30 s. Once in the bloodstream it has minimal protein binding and its pharmacokinetics can be described by a two-compartment model with an α T 1/2 (redistribution) of approximately 7 min and β T 1/2 (elimination) of approximately 2-4 h. [6] Blood levels of approximately 2,000-3,000 ng/ml are required to produce and maintain surgical anesthesia and levels as low as 50-100 ng/ml can produce a dissociative state. [3] Blood concentrations in the range of 370 ng/ml have been shown to decrease pain perception by 50%. [7]

Metabolism takes place in the liver via hepatic microsomal enzymes (CYP3A4, CY2B6, and CYP2C9). [8] First ketamine is N-demethylated to norketamine, which is then hydroxylated and conjugated to form more water-soluble metabolites. There is also a small amount of drug excreted unchanged in the urine.

Mechanism of anesthesia

Ketamine's principal anesthetic action is believed to take place via noncompetitive antagonism of the N-methyl-D-aspartate (NMDA) receptor, which plays a critical role in excitatory neurosynaptic transmission as well as neuronal plasticity. Lodge et al. first elucidated this mechanism in 1983. [9] It is now known that the NMDA receptor is a transmembrane protein complex composed of four subunits. [10] There is a large N-terminal extracellular portion and a shorter intracellular C terminal portion. The 4 subunits are derived from one of the 3 families NR1, NR2, or NR3. The NR1 subunit contains a binding site for glycine, and the NR2 subunit contains a binding site for glutamate. Functionally, the NMDA receptor is an ion channel that permits passage of multiple cations into cells (including sodium and calcium). The channel is particularly permeable to calcium. A number of molecules are able to noncompetitively inhibit the NMDA receptor by plugging the channel pore when it is in an open conformation. These include phencyclidine, thienylcyclohexylpiperidine, and ketamine.

In addition to blocking the NMDA receptor, ketamine has a number of additional pharmacodynamic actions. For example, it binds to opioid receptors including mu (μ), delta (∂), and kappa (Κ). In a knockout mouse model, Sarton et al. demonstrated that it produces analgesic effects via supraspinal opioid receptors. [11] Gupta et al. further elucidated this mechanism, demonstrating that ketamine induces phosphorylation of mitogen-activated protein kinases by 2-3 times that of traditional opioid drugs. [12]

There is also evidence that ketamine produces its analgesic effects via central nervous system muscarinic receptors. Morita et al. showed that repeated doses lead to upregulation of muscarinic acetylcholine receptors in the central nervous system of mice. [13] Ketamine also effects other ion channels including sodium channels and voltage sensitive calcium channels leading to local anesthetic and gabapentin like effects. [14],[15]

Cardio-vascular effects

Ketamine is a potentially useful anesthetic drug in patients with impaired ventricular function because it has sympathomimetic properties that may augment cardiac output. Johnstone published one of the largest early reports of ketamine's cardiovascular effects in humans. In a study of 45 "relatively fit" patients ranging from 19 to 36 years of age who had the noncardiovascular surgery, he concluded that ketamine was a direct myocardial stimulant whose effects could be blocked using verapamil. [16]

In a more contemporary evaluation of ketamine's cardiovascular effects, Sigtermans et al. found that ketamine increases cardiac output in healthy volunteers by 40-50% at blood concentrations of 40-320 ng/ml. [7] The sentence that begins "Ketamine's mechanism for increasing" should read as follows: "Ketamine's mechanism for increasing cardiac output remains controversial though some studies have suggested that it is a direct myocardial depressant which augments cardiac output through indirect mechanisms such as potentiation of catecholamines. Ketamine's mechanism for increasing cardiac output remains somewhat controversial though as some studies have suggested that ketamine is a direct myocardial depressant that augments cardiac output through indirect mechanisms such as potentiation of catecholamines. [17],[18] Other studies; however, have demonstrated direct positive ionotropic effects of ketamine on human myocytes. [19]

The important question is whether ketamine's cardiovascular effects are different in healthy volunteers and the critically ill. Our literature review supports the idea that its effects are dependent upon the degree of illness. Waxman et al. studied ketamine as an induction drug in a cohort of critically ill surgical patients (doses ranged from 25 mg to 140 mg) and found that ketamine increased heart rate and decreased total body oxygen consumption (VO 2 ). [20] However, its effects on mean arterial pressure (MAP), ventricular performance, and systemic vascular resistance (SVR) were less consistent with approximately half of patients experiencing decreases in MAP, SVR, and ventricular performance after induction. Similarly, Marlow et al. found that in coronary artery bypass patients, ketamine (2 mg/kg) caused significant decreases in stroke volume when used as an induction agent. [21] The magnitude of the decrease appears to have been insignificant though as no patient in the cohort required intervention.

Adverse effects

Despite ketamine's previously mentioned advantages as an anesthetic drug in patients with impaired ventricular function, it has a number of important side effects that have limited its wide spread use. First, it predictably leads to tachycardia, which can be harmful in patients with stenotic heart lesions or coronary artery disease. In an animal model, ketamine increased myocardial oxygen consumption by up to 50%. [22] It may also increase the arrhythmogenic potential of epinephrine, a drug that is commonly used for hemodynamic support during cardiac surgery. [23]

Perhaps the most significant concern that has prevented wider adoption of ketamine as an anesthetic and sedative agent is emergence delirium and the drug's potentially unpleasant psychotropic effects. In his original description of ketamine use in humans, Domino described a side effect rate of 1 in 3 subjects with many patients experiencing strange feelings of floating in space or not being able to feel their bodies. [3] In a recent systematic review of 30 ketamine trials, the rate of hallucinations was 7.4% in patients who received the drug compared to 3.7% in controls. [24] Benzodiazepine premedication appeared to have no protective effect. This same review found that in 13 trials, the rate of nightmares was 2.4% in those who received ketamine compared to 0.8% in controls. Interestingly, 8 trials also demonstrated that 18.2% of patients who received ketamine had pleasant dreams compared to 9.7% of controls.

Intraoperative ketamine use in cardiac surgery

The current body of literature regarding ketamine use in cardiac surgery is not robust; however, there have been a number of important trials. [Table 1] summarizes the clinical studies published since 1990. These trials can be categorized by the outcomes that they investigated, which are the following: (1) Effects on levels of inflammatory biomarkers (2) effects on postoperative pain and patient satisfaction (3) effects on hemodynamic variables and myocardial injury (4) effects on pulmonary function (5) miscellaneous outcome measures.
Table 1: Studies using ketamine in cardiac surgery patients


Click here to view


Our literature review identified seven trials that examined ketamine's effects on inflammatory biomarkers including C-reactive protein (CRP), interleukins (IL) 6, 8, and 10, and tumor necrosis factor alpha. [25],[26],[27],[28],[29],[30],[31] Six trials showed significantly lower inflammatory biomarkers in CPB patients who received ketamine. One of the trials correlated lower CRP levels with a decreased risk of delirium and another correlated lower CRP with improved cognitive outcomes.

Only one trial examined ketamine's effect on poststernotomy pain and overall patient satisfaction. [32] This trial showed no improvement in overall pain scores compared to placebo; however patient satisfaction was improved, and there was significant postoperative opioid sparing with ketamine use. Four trials evaluated ketamine's effects on postoperative myocardial injury through either troponin levels or electrocardiogram criteria. [28],[33],[34],[35] Two of these trials suggested that ketamine decreases myocardial injury after surgery.

One study examined hemodynamic response to ketamine in cardiac surgery patients. [36] This study found that ketamine provided satisfactory hemodynamics during induction, but commonly led to tachycardia. The one study that examined ketamine's effect on postoperative pulmonary complications found no benefit (extubation time or oxygenation indices). [37] Finally, one study examined postoperative quantitative electroencephalogram (EEG) (as a surrogate for brain dysfunction), one study examined postoperative ventricular arrhythmias, and one study examined neutrophil activation after surgery. [38],[39],[40] In these studies ketamine had no effect on postoperative EEG, it decreased the incidence of ventricular arrhythmias, and it decreased neutrophil activation.

Ketamine in the cardiac surgery Intensive Care Unit

Ketamine would seem to be an excellent choice for ICU sedation and pain management in postcardiac surgery patients given its stable hemodynamic profile, minimal respiratory depression, and potent analgesic properties. However, it has not gained widespread acceptance in this setting, possibly because of concerns about its psychogenic profile. In the most recent pain, agitation, delirium guidelines from the Society for Critical Care Medicine it was only recommend as a second line analgesic agent and was not even listed as a "sedative" agent. [41] The guideline goes on to state that there are "two low-quality studies comparing clinical outcomes in those receiving dexmedetomidine and propofol for sedation and that there are no studies comparing clinical outcomes in those receiving ketamine or other sedative agents." The guidelines recommend propofol and dexmedetomidine as first line agents, but this is based primarily upon trials that compare these drugs against benzodiazepines, which showed longer length of ICU stay and mechanical ventilation in those who receive benzodiazepines.

In the adult burn ICU and general surgical ICU, ketamine has been studied sparingly but has been found to be an acceptable sedative and analgesic agent with minimal impact on hemodynamics and respiratory effort. [42],[43] Surprisingly, our literature review identified only two studies of ketamine use in the adult cardiac surgery ICU [Table 1]. These studies, both by Piper et al., showed that ketamine improved postoperative patient satisfaction, postoperative recovery and decreased the incidence of shivering, nausea, and vomiting after CABG surgery. [44],[45]

The paucity of studies examining ketamine as a sedative and analgesic agent in the cardiac surgery unit is surprising given the drug's excellent hemodynamic profile. We believe that ketamine has the potential to be an excellent drug for patients with ventricular assist devices, patients requiring veno-arterial extracorporeal membrane oxygenation for cardiogenic shock, and for other postcardiac surgery patients with poor ventricular function. Ketamine could also be an excellent sedative and analgesic agent for patients with an open chest and refractory right ventricular failure or in patients with high opioid requirements who are being weaned from opioids. [46],[47]

Potential opportunities for ketamine in cardiac surgery and the cardiac surgery Intensive Care Unit

A number of opportunities remain for ketamine to be studied in cardiac surgery patients. The current literature supports the idea that ketamine attenuates the inflammatory response to cardiac surgery with CPB. Whether this consistently leads to improved clinical outcomes remains unclear. Furthermore, not all patients who undergo CPB develop the systemic inflammatory response syndrome, but perhaps ketamine could be useful as an anti-inflammatory drug in high-risk patients who have prolonged exposure to CPB. As previously mentioned ketamine also has the potential to be an excellent sedative and analgesic for patients with postcardiotomy shock; however, the risk of a negative psychotropic experience must always be considered and the risk must be weighed against the risks of using other agents, which may cause systemic hypotension (e.g.,: Propofol and dexmedetomidine).

Other areas where ketamine could potentially prove beneficial include neuroprotection during deep hypothermic circulatory arrest and spinal cord protection during descending thoracic aortic surgery. The role of ketamine as a neuroprotective agent remains particularly complex and uncertain at the present time and requires further clarification in clinical trials. On the one hand, it has been shown that excessive NMDA receptor agonism is harmful in the setting of neurologic injury. [48] This would seem to make ketamine an ideal neuroprotective agent during planned ischemic insults. On the other hand, there are concerns that ketamine increases cerebral blood flow and intracranial pressure (ICP). In a recent review of randomized controlled trials, Himmelseher and Durieux concluded that under conditions of controlled mechanical ventilation ketamine does not increase ICP. [49] In the same review, he concluded that "although a wealth of animal and cellular studies demonstrate neuroprotective effects, virtually no clinical trial data are available" to validate ketamine as a neuroprotective agent. There is also the potential problem that ketamine's psychotropic effects could make an early evaluation of neurologic status challenging after surgery.

Finally, ketamine could prove to be a beneficial adjunct in preventing chronic poststernotomy pain and depression, which occur at relatively high rates after cardiac surgery. [50],[51] Early trials have not shown that ketamine can reliably prevent postthoracotomy pain; however, to our knowledge no trial has examined its effects on poststernotomy pain or chronic pain due to internal mammary artery harvest. [52],[53] Recently ketamine has been shown to be highly effective in treating refractory depression. [54] Future studies may help to determine whether it can also help to decrease the incidence of postcardiac surgery depression.


   Summary Top


Ketamine remains a useful and unique drug in cardiac anesthesia that can provide excellent hemodynamic stability during induction of general anesthesia in patients with poor ventricular function. However, it commonly causes tachycardia that can be detrimental in patients with coronary artery disease or stenotic heart lesions. It has been shown to attenuate the inflammatory response to CPB, but the correlation with clinical benefits remains uncertain. It also has potential use in the postcardiac surgery ICU because of its excellent hemodynamic profile, minimal respiratory depression, and potent analgesic properties. However, at this time there is a paucity of studies to support its use in this setting. Future studies comparing ketamine to other commonly accepted sedative regiments, such as propofol and dexmedetomidine are critically needed in cardiac surgery patients.



 
   References Top

1.
Loix S, De Kock M, Henin P. The anti-inflammatory effects of ketamine: State of the art. Acta Anaesthesiol Belg 2011;62:47-58.  Back to cited text no. 1
    
2.
Dale O, Somogyi AA, Li Y, Sullivan T, Shavit Y. Does intraoperative ketamine attenuate inflammatory reactivity following surgery? A systematic review and meta-analysis. Anesth Analg 2012;115:934-43.  Back to cited text no. 2
    
3.
Domino EF. Taming the ketamine tiger 1965. Anesthesiology 2010;113:678-84.  Back to cited text no. 3
    
4.
Domino EF, Chodoff P, Corssen G. Pharmacologic effects of CI-581, a new dissociative anesthetic, in man. Clin Pharmacol Ther 1965;6:279-91.  Back to cited text no. 4
[PUBMED]    
5.
McNulty JP, Hahn K. Compounded oral ketamine. Int J Pharm Compd 2012;16:364-8.  Back to cited text no. 5
    
6.
Clements JA, Nimmo WS. Pharmacokinetics and analgesic effect of ketamine in man. Br J Anaesth 1981;53:27-30.  Back to cited text no. 6
[PUBMED]    
7.
Sigtermans M, Dahan A, Mooren R, Bauer M, Kest B, Sarton E, et al. S(+)-ketamine effect on experimental pain and cardiac output: A population pharmacokinetic-pharmacodynamic modeling study in healthy volunteers. Anesthesiology 2009;111:892-903.  Back to cited text no. 7
    
8.
Mössner LD, Schmitz A, Theurillat R, Thormann W, Mevissen M. Inhibition of cytochrome P450 enzymes involved in ketamine metabolism by use of liver microsomes and specific cytochrome P450 enzymes from horses, dogs, and humans. Am J Vet Res 2011;72:1505-13.  Back to cited text no. 8
    
9.
Lodge D, Ands NA, Berry SC, Burton NR. Arylcyclohexylamines selectively reduce excitation of mammalian neurons by aspartate-like amino acids. In: Kamenka JM, Domino EF, Geneste P, editors. Phenyclidine and Related Arylcyclohexylamines. Ann Arbor: NPP Books; 1983. p. 595-616.  Back to cited text no. 9
    
10.
Paoletti P, Neyton J. NMDA receptor subunits: Function and pharmacology. Curr Opin Pharmacol 2007;7:39-47.  Back to cited text no. 10
    
11.
Sarton E, Teppema LJ, Olievier C, Nieuwenhuijs D, Matthes HW, Kieffer BL, et al. The involvement of the mu-opioid receptor in ketamine-induced respiratory depression and antinociception. Anesth Analg 2001;93:1495-500.  Back to cited text no. 11
    
12.
Gupta A, Devi LA, Gomes I. Potentiation of μ-opioid receptor-mediated signaling by ketamine. J Neurochem 2011;119:294-302.  Back to cited text no. 12
    
13.
Morita T, Hitomi S, Saito S, Fujita T, Uchihashi Y, Kuribara H. Repeated ketamine administration produces up-regulation of muscarinic receptors in the forebrain and reduces behavioral sensitivity to scopolamine in mice. Psychopharmacology (Berl) 1995;117:396-402.  Back to cited text no. 13
    
14.
Frenkel C, Urban BW. Molecular actions of racemic ketamine on human CNS sodium channels. Br J Anaesth 1992;69:292-7.  Back to cited text no. 14
    
15.
Krupitsky EM, Burakov AM, Romanova TN, Grinenko NI, Grinenko AY, Fletcher J, et al. Attenuation of ketamine effects by nimodipine pretreatment in recovering ethanol dependent men: Psychopharmacologic implications of the interaction of NMDA and L-type calcium channel antagonists. Neuropsychopharmacology 2001;25:936-47.  Back to cited text no. 15
    
16.
Johnstone M. The cardiovascular effects of ketamine in man. Anaesthesia 1976;31:873-82.  Back to cited text no. 16
[PUBMED]    
17.
Gelissen HP, Epema AH, Henning RH, Krijnen HJ, Hennis PJ, den Hertog A. Inotropic effects of propofol, thiopental, midazolam, etomidate, and ketamine on isolated human atrial muscle. Anesthesiology 1996;84:397-403.  Back to cited text no. 17
    
18.
Cook DJ, Carton EG, Housmans PR. Mechanism of the positive inotropic effect of ketamine in isolated ferret ventricular papillary muscle. Anesthesiology 1991;74:880-8.  Back to cited text no. 18
    
19.
Hanouz JL, Persehaye E, Zhu L, Lammens S, Lepage O, Massetti M, et al. The inotropic and lusitropic effects of ketamine in isolated human atrial myocardium: The effect of adrenoceptor blockade. Anesth Analg 2004;99:1689-95.  Back to cited text no. 19
    
20.
Waxman K, Shoemaker WC, Lippmann M. Cardiovascular effects of anesthetic induction with ketamine. Anesth Analg 1980;59:355-8.  Back to cited text no. 20
[PUBMED]    
21.
Marlow R, Reich DL, Neustein S, Silvay G. Haemodynamic response to induction of anaesthesia with ketamine/midazolam. Can J Anaesth 1991;38:844-8.  Back to cited text no. 21
    
22.
Patschke D, Brückner JB, Gethmann JW, Tarnow J, Weymar A. The effect of ketamine on haemodynamics and myocardial oxygen consumption in anaesthetized dogs (author's transl). Prakt Anaesth 1975;10:325-34.  Back to cited text no. 22
    
23.
Koehntop DE, Liao JC, Van Bergen FH. Effects of pharmacologic alterations of adrenergic mechanisms by cocaine, tropolone, aminophylline, and ketamine on epinephrine-induced arrhythmias during halothane-nitrous oxide anesthesia. Anesthesiology 1977;46:83-93.  Back to cited text no. 23
[PUBMED]    
24.
Elia N, Tramèr MR. Ketamine and postoperative pain - A quantitative systematic review of randomised trials. Pain 2005;113:61-70.  Back to cited text no. 24
    
25.
Roytblat L, Talmor D, Rachinsky M, Greemberg L, Pekar A, Appelbaum A, et al. Ketamine attenuates the interleukin-6 response after cardiopulmonary bypass. Anesth Analg 1998;87:266-71.  Back to cited text no. 25
    
26.
Cao DQ, Chen YP, Zou DQ. Effects of katamine on cardiopulmonary bypass-induced interleukin-6 and interleukin-8 response and its significance. Hunan Yi Ke Da Xue Xue Bao 2001;26:350-2.  Back to cited text no. 26
    
27.
Bartoc C, Frumento RJ, Jalbout M, Bennett-Guerrero E, Du E, Nishanian E. A randomized, double-blind, placebo controlled study assessing the anti-inflammatory effects of ketamine in cardiac surgical patients. J Cardiothorac Vasc Anesth 2006;20:217-22.  Back to cited text no. 27
    
28.
Cho JE, Shim JK, Choi YS, Kim DH, Hong SW, Kwak YL. Effect of low-dose ketamine on inflammatory response in off-pump coronary artery bypass graft surgery. Br J Anaesth 2009;102:23-8.  Back to cited text no. 28
    
29.
Hudetz JA, Patterson KM, Iqbal Z, Gandhi SD, Byrne AJ, Hudetz AG, et al. Ketamine attenuates delirium after cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth 2009;23:651-7.  Back to cited text no. 29
    
30.
Hudetz JA, Iqbal Z, Gandhi SD, Patterson KM, Byrne AJ, Hudetz AG, et al. Ketamine attenuates post-operative cognitive dysfunction after cardiac surgery. Acta Anaesthesiol Scand 2009;53:864-72.  Back to cited text no. 30
    
31.
Welters ID, Feurer MK, Preiss V, Muller M, Scholz S, Kwapisz M, et al. Continuous S-(+)-ketamine administration during elective coronary artery bypass graft surgery attenuates pro-inflammatory cytokine response during and after cardiopulmonary bypass. Br J Anaesth 2011;106:172-9.  Back to cited text no. 31
    
32.
Lahtinen P, Kokki H, Hakala T, Hynynen M. S(+)-ketamine as an analgesic adjunct reduces opioid consumption after cardiac surgery. Anesth Analg 2004;99:1295-301.  Back to cited text no. 32
    
33.
Botero CA, Smith CE, Holbrook C, Chavez AM, Snow NJ, Hagen JF, et al. Total intravenous anesthesia with a propofol-ketamine combination during coronary artery surgery. J Cardiothorac Vasc Anesth 2000;14:409-15.  Back to cited text no. 33
    
34.
Neuhäuser C, Preiss V, Feurer MK, Müller M, Scholz S, Kwapisz M, et al. Comparison of S-(+)-ketamine- with sufentanil-based anaesthesia for elective coronary artery bypass graft surgery: Effect on troponin T levels. Br J Anaesth 2008;100:765-71.  Back to cited text no. 34
    
35.
Ríha H, Kotulák T, Brezina A, Hess L, Kramár P, Szárszoi O, et al. Comparison of the effects of ketamine-dexmedetomidine and sevoflurane-sufentanil anesthesia on cardiac biomarkers after cardiac surgery: An observational study. Physiol Res 2012;61:63-72.  Back to cited text no. 35
    
36.
Basagan-Mogol E, Goren S, Korfali G, Turker G, Kaya FN. Induction of anesthesia in coronary artery bypass graft surgery: The hemodynamic and analgesic effects of ketamine. Clinics (Sao Paulo) 2010;65:133-8.  Back to cited text no. 36
    
37.
Parthasarathi G, Raman SP, Sinha PK, Singha SK, Karunakaran J. Ketamine has no effect on oxygenation indices following elective coronary artery bypass grafting under cardiopulmonary bypass. Ann Card Anaesth 2011;14:13-8.  Back to cited text no. 37
[PUBMED]  Medknow Journal  
38.
Smith FJ, Bartel PR, Hugo JM, Becker PJ. Anesthetic technique (sufentanil versus ketamine plus midazolam) and quantitative electroencephalographic changes after cardiac surgery. J Cardiothorac Vasc Anesth 2006;20:520-5.  Back to cited text no. 38
    
39.
Hess WC, Ohe A. Does ketamine/propofol anesthesia possess antiarrhythmogenic quality? A perioperative study in aortocoronary bypass patients. Eur J Med Res 2001;17:543-50.  Back to cited text no. 39
    
40.
Zilberstein G, Levy R, Rachinsky M, Fisher A, Greemberg L, Shapira Y, et al. Ketamine attenuates neutrophil activation after cardiopulmonary bypass. Anesth Analg 2002;95:531-6.  Back to cited text no. 40
    
41.
Barr J, Fraser GL, Puntillo K, Ely EW, Gélinas C, Dasta JF, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med 2013;41:263-306.  Back to cited text no. 41
    
42.
Trupkovic T, Kinn M, Kleinschmidt S. Analgesia and sedation in the intensive care of burn patients: Results of a European survey. J Intensive Care Med 2011;26:397-407.  Back to cited text no. 42
    
43.
Adams HA, Biscoping J, Russ W, Bachmann B, Ratthey K, Hempelmann G. Sedative-analgesic medication in intensive care patients needing ventilator treatment. Anaesthesist 1988;37:268-76.  Back to cited text no. 43
    
44.
Piper SN, Beschmann R, Mengistu A, Kalenka A, Maleck WH, Boldt J. Asessment of recovery, dreaming, hemodynamic, and satisfaction in postcardiac surgery patients receiving supplementary propofol sedation with S ketamine. Minerva Anestesiol 2009;75:363-73.  Back to cited text no. 44
    
45.
Piper SN, Beschmann RB, Mengistu A, Maleck WH, Boldt J, Röhm KD. Postoperative analgosedation with S ketamine decreases the incidences of postanesthetic shivering and nausea and vomiting after cardiac surgery. Med Sci Monit 2008;14:PI59-65.  Back to cited text no. 45
    
46.
Jovaisa T, Laurinenas G, Vosylius S, Sipylaite J, Badaras R, Ivaskevicius J. Effects of ketamine on precipitated opiate withdrawal. Medicina (Kaunas) 2006;42:625-34.  Back to cited text no. 46
    
47.
Luginbühl M, Gerber A, Schnider TW, Petersen-Felix S, Arendt-Nielsen L, Curatolo M. Modulation of remifentanil-induced analgesia, hyperalgesia, and tolerance by small-dose ketamine in humans. Anesth Analg 2003;96:726-32.  Back to cited text no. 47
    
48.
Muir KW, Lees KR. Clinical experience with excitatory amino acid antagonist drugs. Stroke 1995;26:503-13.  Back to cited text no. 48
    
49.
Himmelseher S, Durieux ME. Revising a dogma: Ketamine for patients with neurological injury? Anesth Analg 2005;101:524-34.  Back to cited text no. 49
    
50.
Mazzeffi M, Khelemsky Y. Poststernotomy pain: A clinical review. J Cardiothorac Vasc Anesth 2011;25:1163-78.  Back to cited text no. 50
    
51.
Tully PJ, Baker RA. Depression, anxiety, and cardiac morbidity outcomes after coronary artery bypass surgery: A contemporary and practical review. J Geriatr Cardiol 2012;9:197-208.  Back to cited text no. 51
    
52.
Dualé C, Sibaud F, Guastella V, Vallet L, Gimbert YA, Taheri H, et al. Perioperative ketamine does not prevent chronic pain after thoracotomy. Eur J Pain 2009;13:497-505.  Back to cited text no. 52
    
53.
Ryu HG, Lee CJ, Kim YT, Bahk JH. Preemptive low-dose epidural ketamine for preventing chronic postthoracotomy pain: A prospective, double-blinded, randomized, clinical trial. Clin J Pain 2011;27:304-8.  Back to cited text no. 53
    
54.
Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 2006;63:856-64.  Back to cited text no. 54
    

Top
Correspondence Address:
Dr. Michael Mazzeffi
University of Maryland School of Medicine, 22 South Greene Street S11C00, Baltimore, MD 21201
USA
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-9784.154478

Rights and Permissions



 
 
    Tables

  [Table 1]

This article has been cited by
1 A REVIEW OF KETAMINE ABUSE AND DIVERSION
Sean Sassano-Higgins,Dave Baron,Grace Juarez,Neevon Esmaili,Mark Gold
Depression and Anxiety. 2016; 33(8): 718
[Pubmed] | [DOI]



 

Top