Low-dose ketamine affects immune responses in humans during the early postoperative period

Beilin, Benzion; Rusabrov, Y.; Shapira, Yoram; Roytblat, Leonid; Greemberg, Lev; Yardeni, I. Z.; Bessler, Hanna

doi:10.1093/bja/aem218

Cited by 114 publications

(95 citation statements)

References 36 publications

(24 reference statements)

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“…Several experimental and clinical studies have shown that, in addition to its anesthetic activity and analgesic effects, ketamine exerts anti-inflammatory properties by inhibiting the release of pro inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6 [39][40][41][42][43]. Beilin et al [40] used small doses of ketamine before induction of anaesthesia in patients undergoing abdominal surgery and showed that there was attenuation of secretion of the proinflammatory cytokines IL-6 and TNF alpha, and in preservation of IL-2 production at its preoperative level.…”

Section: Discussionmentioning

confidence: 99%

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Pre-Emptive Analgesia with Ketamine for Relief of Postoperative Pain After Surgical Removal of Impacted Mandibular Third Molars

Hadhimane

Shankariah

Neswi

2015

J. Maxillofac. Oral Surg.

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Purpose In this study we assessed the clinical efficacy of sub-mucosal injection of ketamine at sub-anesthetic dose of 0.5 mg/kg on post-operative pain, swelling and trismus following surgical extraction of impacted mandibular third molars. Methods Forty bilaterally symmetrical impacted mandibular third molars in 20 patients who required surgical removal were included in the study. Within the same individual, one of the sites received a test medication whereas the other site was used as control. All patients received nerve blocks with local anesthetic (2 % lignocaine hydrochloride with 1:80,000 adrenaline); the Test group received sub-mucosal infiltration of 0.5 mg/kg of ketamine hydrochloride (without preservative) around the impacted mandibular third molar and along the incision line, while the Placebo group received normal saline infiltration, 10 min before placement of the incision. Results The pain scores on VAS at 30 min, 1, 4, 12 h and 1 day post-operatively was significantly lower in the Test group than in the Placebo group (p \ .05). With respect to facial swelling and mouth opening the Test group and Placebo group showed overall no statistically significant difference (p [ .05) on the 1st, 3rd and 7th post-operative days. Conclusion The sub-mucosal injection of 0.5 mg/kg ketamine administered before surgical removal of impacted mandibular third molars was found to be effective in significantly reducing post-operative pain for the first 24 h.

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Section: Discussionmentioning

confidence: 99%

“…Beilin et al [40] used small doses of ketamine before induction of anaesthesia in patients undergoing abdominal surgery and showed that there was attenuation of secretion of the proinflammatory cytokines IL-6 and TNF alpha, and in preservation of IL-2 production at its preoperative level.…”

Section: Discussionmentioning

confidence: 99%

Pre-Emptive Analgesia with Ketamine for Relief of Postoperative Pain After Surgical Removal of Impacted Mandibular Third Molars

Hadhimane

Shankariah

Neswi

2015

J. Maxillofac. Oral Surg.

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“…Thiopentone, diazepam and ketamine have shown to negatively affect NK activity and lung tumor retention [59]. Thiopental and ketamine [94] also inhibit the LPSinduced release of IL-1, IL-6, TNF-α [95] and IL-8, and increase IL-10 [96][97]. In healthy volunteers, thiopentone and etomidate impair lymphocytes function [84].…”

Section: Intravenous Anestheticsmentioning

confidence: 99%

“…Preoperative use of small doses (0.15 mg/kg) of ketamine has been shown to suppress the inflammatory response and release of IL-6 and TNF-α, without altering IL-2 secretion [95]. Etomidate causes inhibition of T-lymphocyte function in vitro [101], but other studies have shown that etomidate does not affect NF-kappa B activation in human T-lymphocytes [102].…”

Section: Intravenous Anestheticsmentioning

confidence: 99%

Anesthesia, cytokines and cancer recurrence

Kitamura¹,

Biaso²,

Ingelmo

et al. 2015

Glob Anesth Perioper Med

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Cytokines are essential mediators for the regulation of both innate and acquired immunity and hematopoiesis. They modulate immune cell signaling, activation, adhesion and functioning. They regulate the individual response to several insults such as infection, inflammation, trauma, and pain. Moreover, the balance between pro-inflammatory and anti-inflammatory cytokines is critical for the evolution of surgical complications and tumor progression.Several drugs, including anesthetic agents, influence cytokines secretion. Opioids, inhalational agents, intravenous and local anesthetics have shown different effects on immune system and cytokine expression. Therefore, anesthesia may play an important role in postoperative recovery and outcome of cancer patients.The aim of the present article is to review the main role of some important cytokines and the effect of anesthesia techniques and drugs on their secretion. Furthermore, current clinical evidence regarding the effects of anesthesia on cancer recurrence will be discussed. Cytokines and immune systemCytokines are proteins expressed in both innate and acquired immune system and are often named according to the secreting cells (i.e., lymphocytes, interleukins, etc.). They are essential mediators of the natural (non-specific, innate) immunity, which is the initial step of the inflammatory response. They also play a pivotal role during the specific immunity, which occurs after exposure to antigens, as they regulate lymphocyte and leukocyte activation, growth and differentiation, and the immune-mediated inflammation [1].The cytokines have different structures, but also common aspects, which are summarized in Table 1.The aim of the present article is to review the main role of some important cytokines and the effect of anesthesia techniques and drugs on their secretion. Cytokines receptorsThe cytokines receptors are formed by one or more transmembrane proteins: the extracellular portion binds the cytokine, whereas the cytoplasmic part starts the signal cascade. Based on the extracellular portion, they are divided in five categories. 1) Type I receptors, which have four α-helical stands and contain four cysteine residues and the amino acid motif tryptophanserine-X-tryptophan-serine (WSXWS).2) Type II receptors, structurally similar to Type I receptors, but without the sequence WSXWS. Cytokines functionProvided that the same cytokine may be produced during both innate and acquired immunity response, cytokines can be classified according to their functions: 1)Cytokines regulating the innate immunity and secreted by stimulated macrophages; 2)Cytokines regulating the acquired immunity and secreted by lymphocytes; 3)Cytokines stimulating the hematopoiesiss and secreted by bone marrow, leucocytes and other cells. Common aspects of CytokineTheir secretion is brief and limited in time Cytokine expressed during the innate immunity response Tumor necrosis factor (TNF-α, TNF-β)The TNF is responsible for the initial phase of acute inflammatory response, especially against ...

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“…A human study showed that low dose ketamine prior to induction of anesthesia prevented a significant suppression of lymphocyte proliferation. 19 Immunological effects appear to be dose-dependent. Animal studies have shown a significant increase in lung tumour retention with larger doses; 16 however, pre-treatment with a beta-blocker reduced this effect, suggesting involvement of ketamine's intrinsic adrenergic stimulating properties.…”

Section: Ketaminementioning

confidence: 99%