ABSTRACT
Dexmedetomidine has been subjected to an extensive evaluation for its’ role in the prevention of postoperative delirium following cardiac surgery. In striking contrast to the preexisting meta-analysis supporting postoperative delirium-reduction with dexmedetomidine, few recently concluded multicentric large scale randomized controlled trials suggest otherwise. This article aims to present a nuanced perspective of the evolving controversy by attempting to decode the apparent incongruences in the literature accumulating off-late, which is particularly pertinent amidst an ever-escalating heterogeneity in the current research ecosystem.
Keywords:
Cardiac Surgery; Dexmedetomidine; Meta-Analysis; Delirium; Randomized Controlled Trials.
Ever since the first report of postoperative delirium (POD) following cardiac surgery in 1964, it remains an ardently researched domain[11 Egerton N, Kay JH. Psychological disturbances associated with open heart surgery. Br J Psychiatry. 1964;110:433-9. doi:10.1192/bjp.110.466.433.
https://doi.org/10.1192/bjp.110.466.433....
2 Kumar AK, Jayant A, Arya VK, Magoon R, Sharma R. Delirium after cardiac surgery: a pilot study from a single tertiary referral center. Ann Card Anaesth. 2017;20(1):76-82. Erratum in: Ann Card Anaesth. 2017;20(2):281. doi:10.4103/0971-9784.197841.
3 Brown CH. Delirium in the cardiac surgical ICU. Curr Opin Anaesthesiol. 2014;27(2):117-22. doi:10.1097/ACO.0000000000000061.
https://doi.org/10.1097/ACO.000000000000...
-44 Magoon R, Kumar AK, Malik V, Makhija N. Dexmedetomidine and postoperative delirium: decoding the evidence! J Anaesthesiol Clin Pharmacol. 2020;36(1):140-1. doi:10.4103/joacp.JOACP_237_19.
https://doi.org/10.4103/joacp.JOACP_237_...
]. This is principally attributed to the fact that the incidence of POD continues to range between 13 and 50% despite major advancements in cardiac surgical conduct[22 Kumar AK, Jayant A, Arya VK, Magoon R, Sharma R. Delirium after cardiac surgery: a pilot study from a single tertiary referral center. Ann Card Anaesth. 2017;20(1):76-82. Erratum in: Ann Card Anaesth. 2017;20(2):281. doi:10.4103/0971-9784.197841.,33 Brown CH. Delirium in the cardiac surgical ICU. Curr Opin Anaesthesiol. 2014;27(2):117-22. doi:10.1097/ACO.0000000000000061.
https://doi.org/10.1097/ACO.000000000000...
]. The POD-associated morbidity-mortality, caregiver suffering, and the healthcare burden buttress the importance of a sound prediction and prevention strategy[11 Egerton N, Kay JH. Psychological disturbances associated with open heart surgery. Br J Psychiatry. 1964;110:433-9. doi:10.1192/bjp.110.466.433.
https://doi.org/10.1192/bjp.110.466.433....
2 Kumar AK, Jayant A, Arya VK, Magoon R, Sharma R. Delirium after cardiac surgery: a pilot study from a single tertiary referral center. Ann Card Anaesth. 2017;20(1):76-82. Erratum in: Ann Card Anaesth. 2017;20(2):281. doi:10.4103/0971-9784.197841.
3 Brown CH. Delirium in the cardiac surgical ICU. Curr Opin Anaesthesiol. 2014;27(2):117-22. doi:10.1097/ACO.0000000000000061.
https://doi.org/10.1097/ACO.000000000000...
-44 Magoon R, Kumar AK, Malik V, Makhija N. Dexmedetomidine and postoperative delirium: decoding the evidence! J Anaesthesiol Clin Pharmacol. 2020;36(1):140-1. doi:10.4103/joacp.JOACP_237_19.
https://doi.org/10.4103/joacp.JOACP_237_...
].
Talking of the pharmacological prevention of POD, dexmedetomidine (DEX) has been subjected to an extensive evaluation with mixed results in the available literature[44 Magoon R, Kumar AK, Malik V, Makhija N. Dexmedetomidine and postoperative delirium: decoding the evidence! J Anaesthesiol Clin Pharmacol. 2020;36(1):140-1. doi:10.4103/joacp.JOACP_237_19.
https://doi.org/10.4103/joacp.JOACP_237_...
,55 Wu M, Liang Y, Dai Z, Wang S. Perioperative dexmedetomidine reduces delirium after cardiac surgery: a meta-analysis of randomized controlled trials. J Clin Anesth. 2018;50:33-42. doi:10.1016/j.jclinane.2018.06.045.
https://doi.org/10.1016/j.jclinane.2018....
6 Wang G, Niu J, Li Z, Lv H, Cai H. The efficacy and safety of dexmedetomidine in cardiac surgery patients: a systematic review and meta-analysis. PLoS One. 2018;13(9):e0202620. doi:10.1371/journal.pone.0202620.
https://doi.org/10.1371/journal.pone.020...
7 Subramaniam B, Shankar P, Shaefi S, Mueller A, O'Gara B, Banner-Goodspeed V, et al. Effect of intravenous acetaminophen vs placebo combined with propofol or dexmedetomidine on postoperative delirium among older patients following cardiac surgery: the DEXACET randomized clinical trial. JAMA. 2019;321(7):686-96. Erratum in: JAMA. 2019;322(3):276. doi:10.1001/jama.2019.0234.-88 Turan A, Duncan A, Leung S, Karimi N, Fang J, Mao G, et al. Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): a randomised placebo-controlled trial. Lancet. 2020;396(10245):177-85. doi:10.1016/S0140-6736(20)30631-0.
https://doi.org/10.1016/S0140-6736(20)30...
]. While a number of existing meta-analyses support POD-reduction with DEX in a cardiac surgical setting[55 Wu M, Liang Y, Dai Z, Wang S. Perioperative dexmedetomidine reduces delirium after cardiac surgery: a meta-analysis of randomized controlled trials. J Clin Anesth. 2018;50:33-42. doi:10.1016/j.jclinane.2018.06.045.
https://doi.org/10.1016/j.jclinane.2018....
,66 Wang G, Niu J, Li Z, Lv H, Cai H. The efficacy and safety of dexmedetomidine in cardiac surgery patients: a systematic review and meta-analysis. PLoS One. 2018;13(9):e0202620. doi:10.1371/journal.pone.0202620.
https://doi.org/10.1371/journal.pone.020...
], few large scale randomized controlled trials (RCTs) conducted off-late suggest otherwise[77 Subramaniam B, Shankar P, Shaefi S, Mueller A, O'Gara B, Banner-Goodspeed V, et al. Effect of intravenous acetaminophen vs placebo combined with propofol or dexmedetomidine on postoperative delirium among older patients following cardiac surgery: the DEXACET randomized clinical trial. JAMA. 2019;321(7):686-96. Erratum in: JAMA. 2019;322(3):276. doi:10.1001/jama.2019.0234.,88 Turan A, Duncan A, Leung S, Karimi N, Fang J, Mao G, et al. Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): a randomised placebo-controlled trial. Lancet. 2020;396(10245):177-85. doi:10.1016/S0140-6736(20)30631-0.
https://doi.org/10.1016/S0140-6736(20)30...
]. In this context, “Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE)” - the placebo-controlled RCT by Turan et al.[88 Turan A, Duncan A, Leung S, Karimi N, Fang J, Mao G, et al. Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): a randomised placebo-controlled trial. Lancet. 2020;396(10245):177-85. doi:10.1016/S0140-6736(20)30631-0.
https://doi.org/10.1016/S0140-6736(20)30...
] contemplated across six academic hospitals in the United State of America and later published in The Lancet in the year 2020 - captivates attention. The DECADE trial studying atrial fibrillation and POD co-primarily randomized 798 patients to receive either DEX or saline infusion at 0.1 µg/kg/hour prior to incision, escalated to 0.2 µg/kg/hour at the end of bypass and to 0.4 µg/kg/hour postoperatively till 24 hours. Following the analysis of data of 794 patients, the trial failed to outline an amelioration of either of the unfavorable outcomes, rather demonstrated a non-significant worsening of POD (17% and 12% in the DEX and placebo groups, respectively)[88 Turan A, Duncan A, Leung S, Karimi N, Fang J, Mao G, et al. Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): a randomised placebo-controlled trial. Lancet. 2020;396(10245):177-85. doi:10.1016/S0140-6736(20)30631-0.
https://doi.org/10.1016/S0140-6736(20)30...
]. This portrays a striking contradiction to the findings of the previous meta-analysis of the decade, quite literally[55 Wu M, Liang Y, Dai Z, Wang S. Perioperative dexmedetomidine reduces delirium after cardiac surgery: a meta-analysis of randomized controlled trials. J Clin Anesth. 2018;50:33-42. doi:10.1016/j.jclinane.2018.06.045.
https://doi.org/10.1016/j.jclinane.2018....
,66 Wang G, Niu J, Li Z, Lv H, Cai H. The efficacy and safety of dexmedetomidine in cardiac surgery patients: a systematic review and meta-analysis. PLoS One. 2018;13(9):e0202620. doi:10.1371/journal.pone.0202620.
https://doi.org/10.1371/journal.pone.020...
,88 Turan A, Duncan A, Leung S, Karimi N, Fang J, Mao G, et al. Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): a randomised placebo-controlled trial. Lancet. 2020;396(10245):177-85. doi:10.1016/S0140-6736(20)30631-0.
https://doi.org/10.1016/S0140-6736(20)30...
].
Premised on the evolving controversy, an updated meta-analysis was contemplated by Li et al.[99 Li P, Li LX, Zhao ZZ, Xie J, Zhu CL, Deng XM, et al. Dexmedetomidine reduces the incidence of postoperative delirium after cardiac surgery: a meta-analysis of randomized controlled trials. BMC Anesthesiol. 2021;21(1):153. doi:10.1186/s12871-021-01370-1.
https://doi.org/10.1186/s12871-021-01370...
] comprising of a total of 2,813 adult patients across 15 RCTs (each featuring comparative DEX and placebo-control/other anesthetic-control groups and POD as a primary/secondary outcome) which also included patients of the DECADE trial[88 Turan A, Duncan A, Leung S, Karimi N, Fang J, Mao G, et al. Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): a randomised placebo-controlled trial. Lancet. 2020;396(10245):177-85. doi:10.1016/S0140-6736(20)30631-0.
https://doi.org/10.1016/S0140-6736(20)30...
]. The pooled results emanating from this very recent meta-analysis published in 2021 revealed that DEX could significantly attenuate the risk of POD in comparison to the controls, with an odds ratio (OR) of 0.56, 95% confidence interval (CI) of 0.36-0.89, P-value = 0.0004, and 64% I2 coefficient[99 Li P, Li LX, Zhao ZZ, Xie J, Zhu CL, Deng XM, et al. Dexmedetomidine reduces the incidence of postoperative delirium after cardiac surgery: a meta-analysis of randomized controlled trials. BMC Anesthesiol. 2021;21(1):153. doi:10.1186/s12871-021-01370-1.
https://doi.org/10.1186/s12871-021-01370...
]. Ahead of the demonstration of 44% POD risk reduction with DEX, the total POD-incidence funnel plot did not connote a significant publication bias in the meta-analysis. The additional findings of the subgroup analysis are outlined in Table 1[99 Li P, Li LX, Zhao ZZ, Xie J, Zhu CL, Deng XM, et al. Dexmedetomidine reduces the incidence of postoperative delirium after cardiac surgery: a meta-analysis of randomized controlled trials. BMC Anesthesiol. 2021;21(1):153. doi:10.1186/s12871-021-01370-1.
https://doi.org/10.1186/s12871-021-01370...
].
Findings of the subgroup analysis of the Li et al. meta-analysis[99 Li P, Li LX, Zhao ZZ, Xie J, Zhu CL, Deng XM, et al. Dexmedetomidine reduces the incidence of postoperative delirium after cardiac surgery: a meta-analysis of randomized controlled trials. BMC Anesthesiol. 2021;21(1):153. doi:10.1186/s12871-021-01370-1.
https://doi.org/10.1186/s12871-021-01370... ].
Although the primary conclusions of the DECADE trial and Li et al.[99 Li P, Li LX, Zhao ZZ, Xie J, Zhu CL, Deng XM, et al. Dexmedetomidine reduces the incidence of postoperative delirium after cardiac surgery: a meta-analysis of randomized controlled trials. BMC Anesthesiol. 2021;21(1):153. doi:10.1186/s12871-021-01370-1.
https://doi.org/10.1186/s12871-021-01370...
] meta-analysis appear incongruous at first sight, a closer look resolves the dilemma to an extent[88 Turan A, Duncan A, Leung S, Karimi N, Fang J, Mao G, et al. Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): a randomised placebo-controlled trial. Lancet. 2020;396(10245):177-85. doi:10.1016/S0140-6736(20)30631-0.
https://doi.org/10.1016/S0140-6736(20)30...
]. As described previously, the DECADE trial initiated DEX infusion intraoperatively wherein the absence of an eventual POD reduction is actually consistent with the Li et al.[99 Li P, Li LX, Zhao ZZ, Xie J, Zhu CL, Deng XM, et al. Dexmedetomidine reduces the incidence of postoperative delirium after cardiac surgery: a meta-analysis of randomized controlled trials. BMC Anesthesiol. 2021;21(1):153. doi:10.1186/s12871-021-01370-1.
https://doi.org/10.1186/s12871-021-01370...
] subgroup analysis, which also limits the description of POD-reduction potential to a postoperative drug administration (Table 1)[88 Turan A, Duncan A, Leung S, Karimi N, Fang J, Mao G, et al. Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): a randomised placebo-controlled trial. Lancet. 2020;396(10245):177-85. doi:10.1016/S0140-6736(20)30631-0.
https://doi.org/10.1016/S0140-6736(20)30...
,99 Li P, Li LX, Zhao ZZ, Xie J, Zhu CL, Deng XM, et al. Dexmedetomidine reduces the incidence of postoperative delirium after cardiac surgery: a meta-analysis of randomized controlled trials. BMC Anesthesiol. 2021;21(1):153. doi:10.1186/s12871-021-01370-1.
https://doi.org/10.1186/s12871-021-01370...
]. Li et al.[99 Li P, Li LX, Zhao ZZ, Xie J, Zhu CL, Deng XM, et al. Dexmedetomidine reduces the incidence of postoperative delirium after cardiac surgery: a meta-analysis of randomized controlled trials. BMC Anesthesiol. 2021;21(1):153. doi:10.1186/s12871-021-01370-1.
https://doi.org/10.1186/s12871-021-01370...
] speculate intraoperative hypotension (IOH) as a likely mechanism of lack of POD protection of intraoperative DEX and elaborate that the former was not recorded in many of the included RCTs[99 Li P, Li LX, Zhao ZZ, Xie J, Zhu CL, Deng XM, et al. Dexmedetomidine reduces the incidence of postoperative delirium after cardiac surgery: a meta-analysis of randomized controlled trials. BMC Anesthesiol. 2021;21(1):153. doi:10.1186/s12871-021-01370-1.
https://doi.org/10.1186/s12871-021-01370...
]. Turan et al.[88 Turan A, Duncan A, Leung S, Karimi N, Fang J, Mao G, et al. Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): a randomised placebo-controlled trial. Lancet. 2020;396(10245):177-85. doi:10.1016/S0140-6736(20)30631-0.
https://doi.org/10.1016/S0140-6736(20)30...
] also implicate IOH for the non-significant rise in POD in the DECADE trial given the incidence of the same was 57% and 36% in the DEX and placebo groups, respectively. However, no significant association between IOH and POD materialized in the Wang et al.[1010 Wang J, Mao G, Malackany N, Marciniak D, Donaldson C, Wakefield B, et al. Association between perioperative hypotension and postoperative delirium and atrial fibrillation after cardiac surgery: a post-hoc analysis of the DECADE trial. J Clin Anesth. 2022;76:110584. doi:10.1016/j.jclinane.2021.110584.
https://doi.org/10.1016/j.jclinane.2021....
] post-hoc analysis of the DECADE trial including data from three Cleveland Clinic hospitals, outlining an adjusted OR of 0.94 (95% CI: 0.81-1.09; P-value = 0.419) for a doubling in the area under the curve of mean arterial pressure < 60 mmHg, after applying thorough logistic regression models and adjusting for 11 confounders.
As far as POD reduction with postoperative DEX is concerned, an enlightening discussion transpired in a leading cardiothoracic anesthesia journal, the Journal of Cardiothoracic and Vascular Anesthesia[1111 Abowali HA, Paganini M, Enten G, Elbadawi A, Camporesi EM. Critical review and meta-analysis of postoperative sedation after adult cardiac surgery: dexmedetomidine versus propofol. J Cardiothorac Vasc Anesth. 2021;35(4):1134-42. doi:10.1053/j.jvca.2020.10.022.
https://doi.org/10.1053/j.jvca.2020.10.0...
,1212 Heybati K, Deng J, Zhou F, Ali S. Current evidence demonstrates a significant reduction in the incidence of delirium with postoperative dexmedetomidine versus propofol sedation. J Cardiothorac Vasc Anesth. 2022;36(1):347-8. doi:10.1053/j.jvca.2021.06.026.
https://doi.org/10.1053/j.jvca.2021.06.0...
]. An eleven-RCT meta-analysis by Abowali et al.[1111 Abowali HA, Paganini M, Enten G, Elbadawi A, Camporesi EM. Critical review and meta-analysis of postoperative sedation after adult cardiac surgery: dexmedetomidine versus propofol. J Cardiothorac Vasc Anesth. 2021;35(4):1134-42. doi:10.1053/j.jvca.2020.10.022.
https://doi.org/10.1053/j.jvca.2020.10.0...
] concluded an absence of a statistically meaningful POD reduction with postoperative DEX in comparison to propofol sedation. Nonetheless, Heybati et al.[1212 Heybati K, Deng J, Zhou F, Ali S. Current evidence demonstrates a significant reduction in the incidence of delirium with postoperative dexmedetomidine versus propofol sedation. J Cardiothorac Vasc Anesth. 2022;36(1):347-8. doi:10.1053/j.jvca.2021.06.026.
https://doi.org/10.1053/j.jvca.2021.06.0...
] highlighted that Abowali et al.[1111 Abowali HA, Paganini M, Enten G, Elbadawi A, Camporesi EM. Critical review and meta-analysis of postoperative sedation after adult cardiac surgery: dexmedetomidine versus propofol. J Cardiothorac Vasc Anesth. 2021;35(4):1134-42. doi:10.1053/j.jvca.2020.10.022.
https://doi.org/10.1053/j.jvca.2020.10.0...
] managed to erroneously include two RCTs, one administering DEX intraoperatively with another employing DEX as an adjunct to propofol. Subsequently, Heybati et al.[1212 Heybati K, Deng J, Zhou F, Ali S. Current evidence demonstrates a significant reduction in the incidence of delirium with postoperative dexmedetomidine versus propofol sedation. J Cardiothorac Vasc Anesth. 2022;36(1):347-8. doi:10.1053/j.jvca.2021.06.026.
https://doi.org/10.1053/j.jvca.2021.06.0...
] reanalyzed the data of the remaining nine RCTs only to discover a significant POD reduction with postoperative DEX (random-effects OR of 0.18, 95% CI: 0.05-0.65, with an I2 = 52% denoting a moderate heterogeneity level). Needless to say, the readjusted results were in agreement with the recent Li et al.[99 Li P, Li LX, Zhao ZZ, Xie J, Zhu CL, Deng XM, et al. Dexmedetomidine reduces the incidence of postoperative delirium after cardiac surgery: a meta-analysis of randomized controlled trials. BMC Anesthesiol. 2021;21(1):153. doi:10.1186/s12871-021-01370-1.
https://doi.org/10.1186/s12871-021-01370...
] meta-analysis.
Looking beyond the categorical details of the meta-analysis[1313 Bartels K, Sessler DI. Meta-analyses of clinical trials: are we getting lemonade from lemons? Br J Anaesth. 2022;128(2):233-5. doi:10.1016/j.bja.2021.09.028.
https://doi.org/10.1016/j.bja.2021.09.02...
], there are subtle intricacies of the individual DEX-delirium RCTs which necessitate close consideration[99 Li P, Li LX, Zhao ZZ, Xie J, Zhu CL, Deng XM, et al. Dexmedetomidine reduces the incidence of postoperative delirium after cardiac surgery: a meta-analysis of randomized controlled trials. BMC Anesthesiol. 2021;21(1):153. doi:10.1186/s12871-021-01370-1.
https://doi.org/10.1186/s12871-021-01370...
,1414 Chen H, Mo L, Hu H, Ou Y, Luo J. Risk factors of postoperative delirium after cardiac surgery: a meta-analysis. J Cardiothorac Surg. 2021;16(1):113. doi:10.1186/s13019-021-01496-w.
https://doi.org/10.1186/s13019-021-01496...
15 Li CW, Xue FS, Hu B. Determining association between blood glucose variability and postoperative delirium in acute aortic dissection patients: methodological issues. J Cardiothorac Surg. 2021;16(1):344. doi:10.1186/s13019-021-01715-4.
https://doi.org/10.1186/s13019-021-01715...
16 Guenther U, Theuerkauf N, Frommann I, Brimmers K, Malik R, Stori S, et al. Predisposing and precipitating factors of delirium after cardiac surgery: a prospective observational cohort study. Ann Surg. 2013;257(6):1160-7. doi:10.1097/SLA.0b013e318281b01c.
https://doi.org/10.1097/SLA.0b013e318281...
-1717 Humphreys JM, Denson LA, Baker RA, Tully PJ. The importance of depression and alcohol use in coronary artery bypass graft surgery patients: risk factors for delirium and poorer quality of life. J Geriatr Cardiol. 2016;13(1):51-7. doi:10.11909/j.issn.1671-5411.2016.01.010.
https://doi.org/10.11909/j.issn.1671-541...
]. Table 2 enlists some of the pertinent points to assess while interpreting the results of these RCTs[99 Li P, Li LX, Zhao ZZ, Xie J, Zhu CL, Deng XM, et al. Dexmedetomidine reduces the incidence of postoperative delirium after cardiac surgery: a meta-analysis of randomized controlled trials. BMC Anesthesiol. 2021;21(1):153. doi:10.1186/s12871-021-01370-1.
https://doi.org/10.1186/s12871-021-01370...
,1414 Chen H, Mo L, Hu H, Ou Y, Luo J. Risk factors of postoperative delirium after cardiac surgery: a meta-analysis. J Cardiothorac Surg. 2021;16(1):113. doi:10.1186/s13019-021-01496-w.
https://doi.org/10.1186/s13019-021-01496...
15 Li CW, Xue FS, Hu B. Determining association between blood glucose variability and postoperative delirium in acute aortic dissection patients: methodological issues. J Cardiothorac Surg. 2021;16(1):344. doi:10.1186/s13019-021-01715-4.
https://doi.org/10.1186/s13019-021-01715...
16 Guenther U, Theuerkauf N, Frommann I, Brimmers K, Malik R, Stori S, et al. Predisposing and precipitating factors of delirium after cardiac surgery: a prospective observational cohort study. Ann Surg. 2013;257(6):1160-7. doi:10.1097/SLA.0b013e318281b01c.
https://doi.org/10.1097/SLA.0b013e318281...
-1717 Humphreys JM, Denson LA, Baker RA, Tully PJ. The importance of depression and alcohol use in coronary artery bypass graft surgery patients: risk factors for delirium and poorer quality of life. J Geriatr Cardiol. 2016;13(1):51-7. doi:10.11909/j.issn.1671-5411.2016.01.010.
https://doi.org/10.11909/j.issn.1671-541...
]. For instance, the POD protective role evaluation of DEX in the Turan et al. DECADE trial may have been compounded by the lack of a protocolized anesthetic regime, titration of the study drug, and other sedatives administration at the discretion of the anesthesiologist and disregard to the group-specific cumulative sedative drug dosages being utilized[88 Turan A, Duncan A, Leung S, Karimi N, Fang J, Mao G, et al. Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): a randomised placebo-controlled trial. Lancet. 2020;396(10245):177-85. doi:10.1016/S0140-6736(20)30631-0.
https://doi.org/10.1016/S0140-6736(20)30...
,1818 Magoon R. Implications of practice variability: comment. Anesthesiology. 2020;133(4):943-4. doi:10.1097/ALN.0000000000003465.
https://doi.org/10.1097/ALN.000000000000...
,1919 Magoon R. Precision cardiac anesthesia: welcome aboard! J Cardiothorac Vasc Anesth. 2020;34(9):2551-2. doi:10.1053/j.jvca.2020.02.029.
https://doi.org/10.1053/j.jvca.2020.02.0...
]. At the same time, exempting a formal preoperative cognitive status assessment can pose important concerns as adequate literature exists to suggest preoperative anxiety-depression and low mini-mental state examination score as independent risk-factors for POD following cardiac surgery[1414 Chen H, Mo L, Hu H, Ou Y, Luo J. Risk factors of postoperative delirium after cardiac surgery: a meta-analysis. J Cardiothorac Surg. 2021;16(1):113. doi:10.1186/s13019-021-01496-w.
https://doi.org/10.1186/s13019-021-01496...
15 Li CW, Xue FS, Hu B. Determining association between blood glucose variability and postoperative delirium in acute aortic dissection patients: methodological issues. J Cardiothorac Surg. 2021;16(1):344. doi:10.1186/s13019-021-01715-4.
https://doi.org/10.1186/s13019-021-01715...
16 Guenther U, Theuerkauf N, Frommann I, Brimmers K, Malik R, Stori S, et al. Predisposing and precipitating factors of delirium after cardiac surgery: a prospective observational cohort study. Ann Surg. 2013;257(6):1160-7. doi:10.1097/SLA.0b013e318281b01c.
https://doi.org/10.1097/SLA.0b013e318281...
-1717 Humphreys JM, Denson LA, Baker RA, Tully PJ. The importance of depression and alcohol use in coronary artery bypass graft surgery patients: risk factors for delirium and poorer quality of life. J Geriatr Cardiol. 2016;13(1):51-7. doi:10.11909/j.issn.1671-5411.2016.01.010.
https://doi.org/10.11909/j.issn.1671-541...
]. Notably, the Li et al.[99 Li P, Li LX, Zhao ZZ, Xie J, Zhu CL, Deng XM, et al. Dexmedetomidine reduces the incidence of postoperative delirium after cardiac surgery: a meta-analysis of randomized controlled trials. BMC Anesthesiol. 2021;21(1):153. doi:10.1186/s12871-021-01370-1.
https://doi.org/10.1186/s12871-021-01370...
] meta-analysis excluded the RCTs which did not rule out a preoperative cognitive impairment.
Intricacies of the DEX-delirium RCTs to be considered while interpreting the results[99 Li P, Li LX, Zhao ZZ, Xie J, Zhu CL, Deng XM, et al. Dexmedetomidine reduces the incidence of postoperative delirium after cardiac surgery: a meta-analysis of randomized controlled trials. BMC Anesthesiol. 2021;21(1):153. doi:10.1186/s12871-021-01370-1.
https://doi.org/10.1186/s12871-021-01370... ,1414 Chen H, Mo L, Hu H, Ou Y, Luo J. Risk factors of postoperative delirium after cardiac surgery: a meta-analysis. J Cardiothorac Surg. 2021;16(1):113. doi:10.1186/s13019-021-01496-w.
https://doi.org/10.1186/s13019-021-01496...
15 Li CW, Xue FS, Hu B. Determining association between blood glucose variability and postoperative delirium in acute aortic dissection patients: methodological issues. J Cardiothorac Surg. 2021;16(1):344. doi:10.1186/s13019-021-01715-4.
https://doi.org/10.1186/s13019-021-01715...
16 Guenther U, Theuerkauf N, Frommann I, Brimmers K, Malik R, Stori S, et al. Predisposing and precipitating factors of delirium after cardiac surgery: a prospective observational cohort study. Ann Surg. 2013;257(6):1160-7. doi:10.1097/SLA.0b013e318281b01c.
https://doi.org/10.1097/SLA.0b013e318281... -1717 Humphreys JM, Denson LA, Baker RA, Tully PJ. The importance of depression and alcohol use in coronary artery bypass graft surgery patients: risk factors for delirium and poorer quality of life. J Geriatr Cardiol. 2016;13(1):51-7. doi:10.11909/j.issn.1671-5411.2016.01.010.
https://doi.org/10.11909/j.issn.1671-541... ].
Even from a holistic research standpoint, the traditionally cited evidence hierarchy of meta-analysis over and above multiple and single RCTs is an oversimplistic rendition, mandating a cautious interpretation[1313 Bartels K, Sessler DI. Meta-analyses of clinical trials: are we getting lemonade from lemons? Br J Anaesth. 2022;128(2):233-5. doi:10.1016/j.bja.2021.09.028.
https://doi.org/10.1016/j.bja.2021.09.02...
]. Amidst an ongoing surge in the number of meta-analysis, it becomes imperative to realize that meta-analysis of small RCTs can be conducive to an overestimation of treatment effects, often reformed by larger RCTs which follow[1313 Bartels K, Sessler DI. Meta-analyses of clinical trials: are we getting lemonade from lemons? Br J Anaesth. 2022;128(2):233-5. doi:10.1016/j.bja.2021.09.028.
https://doi.org/10.1016/j.bja.2021.09.02...
]. In conclusion, large scale multicentric RCTs and meta-analysis of varying RCT counts coexist in the present heterogeneous research ecosystem wherein a superficial perusal of the conclusions can be misleading, particularly with the methodological issues, potential biases, and rhetorical presentation techniques being an inexorable part of the vignette[1313 Bartels K, Sessler DI. Meta-analyses of clinical trials: are we getting lemonade from lemons? Br J Anaesth. 2022;128(2):233-5. doi:10.1016/j.bja.2021.09.028.
https://doi.org/10.1016/j.bja.2021.09.02...
,2020 Magoon R, Jose J. Safeguarding anaesthesia research from spin. Br J Anaesth. 2020;125(6):e460-2. doi:10.1016/j.bja.2020.08.042.
https://doi.org/10.1016/j.bja.2020.08.04...
].
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No financial support.
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» https://doi.org/10.1016/j.bja.2021.09.028. -
14Chen H, Mo L, Hu H, Ou Y, Luo J. Risk factors of postoperative delirium after cardiac surgery: a meta-analysis. J Cardiothorac Surg. 2021;16(1):113. doi:10.1186/s13019-021-01496-w.
» https://doi.org/10.1186/s13019-021-01496-w. -
15Li CW, Xue FS, Hu B. Determining association between blood glucose variability and postoperative delirium in acute aortic dissection patients: methodological issues. J Cardiothorac Surg. 2021;16(1):344. doi:10.1186/s13019-021-01715-4.
» https://doi.org/10.1186/s13019-021-01715-4. -
16Guenther U, Theuerkauf N, Frommann I, Brimmers K, Malik R, Stori S, et al. Predisposing and precipitating factors of delirium after cardiac surgery: a prospective observational cohort study. Ann Surg. 2013;257(6):1160-7. doi:10.1097/SLA.0b013e318281b01c.
» https://doi.org/10.1097/SLA.0b013e318281b01c. -
17Humphreys JM, Denson LA, Baker RA, Tully PJ. The importance of depression and alcohol use in coronary artery bypass graft surgery patients: risk factors for delirium and poorer quality of life. J Geriatr Cardiol. 2016;13(1):51-7. doi:10.11909/j.issn.1671-5411.2016.01.010.
» https://doi.org/10.11909/j.issn.1671-5411.2016.01.010. -
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» https://doi.org/10.1053/j.jvca.2020.02.029. -
20Magoon R, Jose J. Safeguarding anaesthesia research from spin. Br J Anaesth. 2020;125(6):e460-2. doi:10.1016/j.bja.2020.08.042.
» https://doi.org/10.1016/j.bja.2020.08.042.
Publication Dates
-
Publication in this collection
05 Dec 2022 -
Date of issue
2023
History
-
Received
01 Jan 2022 -
Accepted
28 Apr 2022