Intraoperative ketamine administration to prevent delirium or postoperative cognitive dysfunction: A systematic review and meta‐analysis

Hovaguimian, Frédérique; Tschopp, Chantal; Beck‐Schimmer, Beatrice; Puhan, Milo A.

doi:10.1111/aas.13168

Cited by 70 publications

(51 citation statements)

References 63 publications

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“…A recent meta-analysis identified six clinical trials which administered sub-hypnotic doses (0.2e0.5 mg kg À1 ) of ketamine on induction and showed that it did not increase the risk of delirium, however the quality of evidence is low because of the risk of study bias and study heterogeneity. 108…”

Section: Perioperative Medications and Deliriummentioning

confidence: 99%

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Postoperative delirium: perioperative assessment, risk reduction, and management

Jin

2020

British Journal of Anaesthesia

365

263

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Postoperative delirium is a relatively common and serious complication. It increases hospital stay by 2e3 days and is associated with a 30-day mortality of 7e10%. It is most prevalent in older patients, those with existing neurocognitive disorders, and those undergoing complex or emergency procedures. Preclinical and clinical research in recent years has uncovered more about the pathophysiology of postoperative delirium and may yield more potential therapeutic options. Using the enhanced recovery pathway framework of risk stratification, risk reduction, and rescue treatment, we have reviewed the current clinical evidence on the validity of delirium prediction scores for the surgical population, the effectiveness of perioperative delirium risk reduction interventions, and management options for established delirium. Effective perioperative interventions include depth of anaesthesia monitoring, intraoperative dexmedetomidine infusion, and multimodal analgesia. Choice of general anaesthetic agent may not be associated with significant difference in delirium risk. Several other factors, such as preoperative fasting, temperature control, and blood pressure management have some association with the risk of postoperative delirium; these will require further studies. Because of the limited treatment options available for established delirium, we propose that risk assessment and perioperative risk reduction may be the most effective approaches in managing postoperative delirium.

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Section: Perioperative Medications and Deliriummentioning

confidence: 99%

“…Meta-analysis 108 Included four clinical trials and showed no significant difference; overall quality of evidence is low. Equivocal, require further studies Depth of anaesthesia monitoring-guided general anaesthetics…”

Section: Intraoperative Use Of Ketaminementioning

confidence: 99%

Postoperative delirium: perioperative assessment, risk reduction, and management

Jin

2020

British Journal of Anaesthesia

365

263

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“…64 Surprisingly, ketamine treatment correlated positively with a reduction in serum C-reactive protein levels, leading the authors to speculate that ketamine causes a decrease in POCD incidence by causing a decrease in inflammation. 65 The author found that preoperative melatonin supplementation may improve the incidence of early POCD. 66 Interestingly, a study suggested that dexmedetomidine treatment during surgery significantly reduced postoperative delerium incidence and offered improved short-term recovery for elderly patients.…”

Section: Pharmaceutical Managementmentioning

confidence: 99%

Postoperative cognitive dysfunction in elderly patients undergoing hip arthroplasty

et al. 2020

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Even after successful hip arthroplasty, elderly patients who have undergone this procedure remain subject to cognitive decline and may collectively develop postoperative cognitive dysfunction (POCD). However, no consensus exists as to the risk factors resulting in a higher likelihood that a patient may present with this complication, and the aetiology of POCD is not well understood. We conducted a systematic review of papers concerning the influence of POCD‐related risk factors in patients undergoing hip arthroplasty but limited the literature search to papers in English. A systematic and electronic search for manuscripts in the PubMed database was performed in order to identify all studies in which the risk factors for POCD were investigated. Articles were also obtained from the authors' files. Keywords for the search were postoperative cognitive dysfunction/change/impairment/decline/deficit, elderly/older/aged patients, and hip arthroplasty/replacement surgery. The evidence published to date suggests that POCD is a multifactorial disease, which includes an individual patient's characteristics, surgery, type of anaesthesia, and pain levels. All of these factors can increase the risk of POCD incidence. There are a number of factors that appear to influence the risk of early cognitive dysfunction after hip arthroplasty. Nevertheless, the specific mechanism and explicit risk factors associated with this cognitive dysfunction are not completely understood. Hip arthroplasty has made it possible for older patients to find relief from pain and improve their function, whereas it also increases the risk for suffering POCD that may affect these patients' quality of life and increase their mortality. Therefore, it is worthwhile investigating the mechanism of POCD in future studies in order to prevent and treat this condition.

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“…These findings raise significant concerns for animal studies in biomedical research as many utilize anesthetics for surgical procedures that may lead to unintended cognitive impairments and/or neurological changes that may confound results if not appropriately accounted for. Preliminary studies show that certain sedative agents can improve (Gertler et al, 2001;Hovaguimian et al, 2018) or worsen (Pandharipande et al, 2006) postoperative outcomes, suggesting that postoperative cognitive dysfunction may be linked to the pharmacodynamics of specific anesthetics rather than surgery or the sedation process itself.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Anesthesia on Adult Hippocampal Neurogenesis

2020

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In animal studies, prolonged sedation with general anesthetics has resulted in cognitive impairments that can last for days to weeks after exposure. One mechanism by which anesthesia may impair cognition is by decreasing adult hippocampal neurogenesis. Several studies have seen a reduction in cell survival after anesthesia in rodents with most studies focusing on two particularly vulnerable age windows: the neonatal period and old age. However, the extent to which sedation affects neurogenesis in young adults remains unclear. Adult neurogenesis in the dentate gyrus (DG) was analyzed in male and female rats 24 h after a 4-h period of sedation with isoflurane, propofol, midazolam, or dexmedetomidine. Three different cell populations were quantified: cells that were 1 week or 1 month old, labeled with the permanent birthdate markers EdU or BrdU, respectively, and precursor cells, identified by their expression of the endogenous dividing cell marker proliferating cell nuclear antigen (PCNA) at the time of sacrifice. Midazolam and dexmedetomidine reduced cell proliferation in the adult DG in both sexes but had no effect on postmitotic cells. Propofol reduced the number of relatively mature, 28-day old, neurons specifically in female rats and had no effects on younger cells. Isoflurane had no detectable effects on any of the cell populations examined. These findings show no general effect of sedation on adult-born neurons but demonstrate that certain sedatives do have drug-specific and sex-specific effects. The impacts observed on different cell populations predict that any cognitive effects of these sedatives would likely occur at different times, with propofol producing a rapid but short-lived impairment and midazolam and dexmedetomidine altering cognition after a several week delay. Taken together, these studies lend support to the hypothesis that decreased neurogenesis in the young adult DG may mediate the effects of sedation on cognitive function.

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Intraoperative ketamine administration to prevent delirium or postoperative cognitive dysfunction: A systematic review and meta‐analysis

Abstract: The effect of ketamine on postoperative delirium remains unclear but its administration may offer some protection towards POCD. Large, well-designed randomised trials are urgently needed to further clarify the efficacy of ketamine on neurocognitive outcomes.

Cited by 70 publications

References 63 publications

Postoperative delirium: perioperative assessment, risk reduction, and management

Postoperative delirium: perioperative assessment, risk reduction, and management

Postoperative cognitive dysfunction in elderly patients undergoing hip arthroplasty

The Effects of Anesthesia on Adult Hippocampal Neurogenesis

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