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Pre-operative methylprednisolone and postoperative delirium

Last post 19 Nov 2018, 5:44 PM by Christopher Clemmesen. 1 replies.
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  •  30 Oct 2018, 3:03 PM 2678

    Pre-operative methylprednisolone and postoperative delirium

    Clemmesen et al. [1] concluded that a single, pre-operative dose of 125 mg methylprednisolone didn’t reduce the severity of postoperative delirium, but reduced the incidence of delirium and the severity of fatigue, after hip fracture surgery in elderly patients. We would like to invite the authors to reply to several comments that we have about their paper.

    Firstly, did the authors monitor the depth of anaesthesia administered? Interindividual sensitivity, and the range of propofol doses used  (3-5 mg.kg-1.hr-1) could have affected the rates of postoperative delirium [2]. Similarly, did the authors administer neuromuscular agents during general anaesthesia, residual block after recovery from which is also associated with postoperative delirium [3]?

    Secondly, do the authors think that additional laboratory tests (eg haemoglobin, albumin, glucose and C-reactive protein, as markers of nutritional status and systemic inflammation) may have yielded further predictive information? 

    Thirdly, do the authors consider that there might have been avoidable intra-individual variation between supervised staff using the subjective Confusion Assessment Method (CAM-S long form) scoring system, that could have been avoided by a single blinded observer conducting all the assessments?

    Finally, could the authors provide further details about the doses, frequencies and durations of the standardised pharmacological therapies (including haloperidol and olanzapine) that they used to prevent and treat postoperative delirium? Since there is evidence that haloperidol can prevent delirium [4], do the authors think that the severity and prevalence of postoperative delirium in their high-risk group might have been underestimated due to their use of this agent?

    Although we congratulate Clemmesen et al. for conducting difficult research in this often overlooked patient group, we think that the preventative effect of   methylprednisolone on postoperative delirium currently remains ambiguous, and look forward to further studies.

     

    W. Sun

    Z. T. Qiu

    The First Affiliated Hospital of Shantou University Medical College,

    Shantou, People's Republic of China.

    Email: qiuzt@stu.edu.cn

     

    No external funding and no competing interests declared.

     

    References

    1. Clemmesen CG, Lunn TH, Kristensen MT, Palm H, Foss NB Effect of a single pre-operative 125 mg dose of methylprednisolone on postoperative delirium in hip fracture patients; a randomised, double-blind, placebo-controlled trial. Anaesthesia 2018; 73: 1353-60.
    2. Radtke FM, Franck M, Lendner J, Kruger S, Wernecke KD, Spies CD Monitoring depth of anaesthesia in a randomized trial decreases the rate of postoperative delirium but not postoperative cognitive dysfunction. British Journal of Anaesthesia 2013; 110 Suppl 1: i98-105.
    3. Oh CS, Rhee KY, Yoon TG, Woo NS, Hong SW, Kim SH Postoperative delirium in elderly patients undergoing hip fracture surgery in the sugammadex era: a retrospective study. Biomedical Research International 2016; 2016: 1054597.
    4. Riegger H, Hollinger A, Seifert B, et al. Baden Prevention and Reduction of Incidence of Postoperative Delirium Trial (PRIDe): a phase IV multicenter, randomized, placebo-controlled, double-blind clinical trial of ketamine versus haloperidol for prevention of postoperative delirium. Trials 2018; 19: 142.
  •  19 Nov 2018, 5:44 PM 2692 in reply to 2678

    Pre-operative methylprednisolone and postoperative delirium - a reply

    We thank Sun and Qiu for theuir constructive enquiries about our paer on pre-operative methylprednisolone and postoperative delirium after hip fracture surgery [1].

    We did not monitor depth of anaesthesia. We agree that monitoring depth of anaesthesia might reduce postoperative delirium after general anaesthesia. However, this assertion is based on only two studies [2], both of which were undertaken in elective surgery involving elderly patients (particularly orthopaedic patients) [3, 4]. Elderly patients with hip fracture might experince a different subtype of postoperative delirium [5], making it difficult to extrapolate from other patient groups. Furthermore, few of the patients in our study received general anaesthesia (22 of 117), with the only neuromuscular agents used during general anaesthesia being suxamethonium, the risk of residual block after which must be considered to be low. As our study was a double blinded randomized controlled trial (RCT), we assume that the randomization process minimised between-group differences. According to CONSORT 2010 statements, it is illogical to perform significance test on baseline differences. 

    We did collect laboratory tests during the trial with the aim of measuring systemic inflammation, and will submit our results for publication in due course. .

    It was not possible to have a single blinded observer to conduct all the assessments. Again the RCT process should havve limited the influence of this between groups. The CAM (as the CAM-S is based on) is a validated measurement tool that has been used for many years at our institution All observers are highly trained and the majority of assessments were undertaken by the same observer, and so we do not think that intra-individual observer variation influenced our results.

    There is no evidence for treating postoperative delirium with pharmacological therapies [6] and so we did not use them preventatively. The use of haloperidol to prevent delirium is also doubtful [7]. Patients with delirium could have received treatment with haloperidol (olanzapine, if contrainduicated), but only after being diagnosed with delirium. We do not think there was any underestimation of deliriumprevalence because of haloperidol administration. However, the severity of delirium may have been estimated, but this should have occurred similarly between groups. 

    We agree that the preventative effect of methylprednisolone is not conclusive after our single study on a selective patient group. A large safety study on high-dose glucocorticoid in primary total knee replacement did not find any safety issues with the use of preoperative glucocorticoids [8]. Taken together, we believe that these studies indicate that other studies involving methylprednisolone administration to elderly patients with hip fracture are warranted.

     

    C. Clemmesen

     On behalf of the authors

     

    Copenhagen University Hospital,

    Hvidovre, Denmark.

    Email: cclemmesen@gmail.com

     

    No external funding and no conflicts of interest declared.

     

    References

    1. Clemmesen CG, Lunn TH, Kristensen MT, Palm H, Foss NB Effect of a single pre-operative 125 mg dose of methylprednisolone on postoperative delirium in hip fracture patients; a randomised, double-blind, placebo-controlled trial. Anaesthesia 2018; 73: 1353-60.

    2. Siddiqi N, Harrison JK, Clegg A, Teale EA, Young J, Taylor J, Simpkins SA. Interventions for preventing delirium in hospitalised non-ICU patients. Cochrane Database of Systematic Reviews 2016; 3: CD005563.

    3. Chan MT, Cheng BC, Lee TM, Gin T and the CODA Trial Group. BIS‐guided anesthesia decreases postoperative delirium and cognitive decline. Journal of Neurosurgical Anesthesiology 2013; 25: 33‐42.

    4. Radtke FM, Franck M, Lendner J, Kruger S, Wernecke KD, Spies CD. Monitoring depth of anaesthesia in a randomized trial decreases the rate of postoperative delirium but not postoperative cognitive dysfunction. British Journal of Anaesthesia 2013;110 suppl. 1: i98‐105.

    5. Brauer C, Morrison RS, Silberzweig SB, Siu AL. The cause of delirium in patients with hip fracture. Archives of Internal Medicine 2000; 160: 1856-60.

    6. Burry L, Mehta S, Perreault MM, Luxenberg JS, Siddiqi N, Hutton B, Fergusson DA, Bell C, Rose L. Antipsychotics for treatment of delirium in hospitalised non-ICU patients. Cochrane Database of Systematic Reviews 2018; 6: CD005594.

    7. Teale EA. Haloperidol for delirium prevention: uncertainty remains. Age and Ageing 2018; 47: 3-5.

    8. Jørgensen CC, Pitter FT, Kehlet H, on behalf of the Lundbeck Foundation Center for Fast-track Hip and Knee Replacement Collaborative Group. Safety aspects of preoperative high-dose glucocorticoid in primary total knee replacement. British Journal of Anaesthesia 2017; 119: 267-75.

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