THE IMPACT OF DIFFERENT TYPES OF PAIN MANAGEMENT ...

NEUROLOGY | REVIEW ARTICLE

THE IMPACT OF DIFFERENT TYPES OF PAINMANAGEMENT MODALITIES ON POST-OPERATIVE

DELIRIUMNarayan Bhetwal∗�,1, Jeannie Rivers∗�, Thomas Miller∗�, Michael Amendola∗�, Kellenn Cresswell4, Adam Sima4 and Lucretia

Wright∗∗Surgical Service, Hunter Holmes McGuire Veteran Affairs Medical Center, 1201 Broad Rock Blvd, Richmond, Virginia 23249, �. Department of Surgery,

Virginia Commonwealth University Medical Center, Richmond, Virginia 23298., 4Department of Biostatistics, Virginia Commonwealth University, Richmond,VA,23298.

ABSTRACT Importance:Delirium is a common problem in patients undergoing surgery. Evidence suggests that the typeof anaesthesia used, and postoperative pain management approach can impact the frequency of delirium, but there is noconsensus on this issue. Objectives:This study explored the role of peri-operative pain management modalities, includingnerve block, in managing postoperative pain and their association with the development of delirium. Design:This isa retrospective cohort study of 440 patients who underwent lower limb amputations and hip, and knee arthroplastiesbetween January 2010 and December 2017 were reviewed. Setting:Charts of patients who underwent surgery and wereadmitted to the Hunter Holmes McGuire VA Medical Center, Richmond, VA, were reviewed. Participants:A total of 460charts were reviewed (20 were excluded) of patients undergoing total hip arthroplasty, above knee amputation, totalknee arthroplasty, below-knee amputation and trans metatarsal amputation. Delirium, as a problem in the postoperativeperiod had to be clearly stated in the patient’s record. Main outcome:Development of delirium during the postoperativeperiod in association with the different types of pain management strategies. Results: A total of 60 patients (13.6%) fromthe 440 studied developed postoperative delirium among the different pain management strategies [(IV Acetaminophen,gabapentin, oral narcotics, patient-controlled analgesia, and non-steroidal anti-inflammatory drugs (NSAIDs)], onlygabapentin was associated with delirium, demonstrating a 2.27 times higher risk (P=0.0085). We also found that priornarcotic use increased the odds of delirium (P=0.0053). Even after controlling for the anaesthesia type (general, local,regional, spinal and epidural), no association between nerve block and delirium was observed (P=0.41). Conclusion andRelevance: Taking gabapentin post-operatively for pain management and having a history of ongoing narcotic usageprior to surgery, were associated with a higher risk of developing delirium. We found no association between nerve blockused and the development of delirium.

KEYWORDS Delirium, Postoperative Pain, Gabapentin, Nerve block, Orthopedic procedures.

Copyright © 2020 by the Bulgarian Association of Young SurgeonsDOI:10.5455/ijsm.Pain-Management-deliriumFirst Received: September 20, 2020Accepted: November 14, 2020Associate Editor: Ivan Inkov (BG);1Surgical Service, Hunter Holmes McGuire Veteran Affairs Medical Center, 1201Broad Rock Blvd, Richmond, Virginia 23249. E-mail: [email protected]:0000-0001-9892-7661

Narayan Bhetwal et al./ International Journal of Surgery and Medicine (2021) 7(1):1-9

Introduction

A substantial number of patients develop confusion, acutemetabolic encephalopathy, delirium or mental status changespost operatively, collectively called Post-Operative CognitiveDysfunction (POCD). Delirium, a major component of this des-ignation, occurs in 7-75% of the older hospitalized population.It can go unrecognized in as many as 32-66% of patients havingthis problem depending upon the definition, population beingstudied, type of surgery and assessment tools used to defineits existence. [1,2,3,4] There are both immediate and long-termnegative outcomes associated with delirium. The readmissionrate for postoperative patients experiencing delirium is higherthan patients who do not suffer from the problem. Further,postoperative delirium is associated with an average increase inthe length of hospital stay (LOS) approaching five days.[5] Thesystemic review has suggested that general anaesthesia may beassociated with an increased risk of delirium when compared toregional anesthesia within 7 days of the surgery performed.[2,6]Interestingly, some studies have shown that the use of regionalanesthesia does not appear to decrease the incidence of deliriumwhen compared with general anesthesia. [7,8] Of further note,it was found that nonopioid pain management techniques, lim-iting narcotics to the oral formulation and avoiding morphine,appear to reduce the risk of delirium.[2] Even though there havebeen many studies pertaining to the type of anesthesia usedand resultant delirium, there is limited research regarding theeffects of different pain management modalities inducing delir-ium, and specifically the use of nerve block as a postoperativepain management strategy.[2],[3] In our institution, there hasbeen an increase in the use of peri-operative nerve block for painmanagement in surgical patients since early 2015. As such, wedecided to evaluate this approach to postoperative pain controland its association with delirium. We hypothesized that the useof nerve block, which might be in the form of one injection ornerve catheter, as postoperative pain management would de-crease opioid use and thus decrease delirium. In addition, wewere interested in determining whether different methods ofpain control influenced the incidence of delirium. This papersummarizes our findings.

Material and Methods:

After approval from our Institutional Review Board (IRB) toconduct this study, we commenced reviewing patient chartsfrom the electronic medical record of the Department of VeteransAffairs, known as the Computerized Patient Record System(CPRS). We downloaded records of patients who underwent fivespecific procedures from January 2010 to December 2017. Wewanted to evaluate procedures in which a nerve block was usedfor postoperative pain management to determine what role itmight play in inducing delirium.

The following procedures were included in the study.

1. Total hip arthroplasty (THA).

2. Above-knee amputation (AKA).

3. Total knee arthroplasty (TKA).

4. Below knee amputation (BKA)

5. Trans metatarsal amputation (TMT).

A total of 460 charts were reviewed of patients undergoingthese various procedures. Out of this number, 440 patients wereincluded in our study. From this sample, we were able to identifywhich patients did or did not develop delirium during postop-erative treatment. To diagnose a case of delirium, evidence ofdelirium as a problem in the postoperative period had to beclearly stated in the record through notes in the patient’s chart.These notes could be written by attendings, residents and/orregistered nurses caring for the patient, and sometimes in thepsychiatry and neurology notes, if such specialties were con-sulted. Equally important were notes indicating the absence ofthis problem in patients who did not experience delirium. Inthe 20 patients excluded from the study, there was too muchambiguity in the notes to know for certain whether deliriumwas or was not present in the postoperative period.

In the 440 patients making up this study, several variableswere evaluated. (See Tables 1, 2, 3, and 4a and 4b). After re-viewing the data, it was submitted to the Statistical AnalysisCenter of the Biostatistics Consulting Laboratory, Departmentof Biostatistics, School of Medicine at Virginia CommonwealthUniversity in Richmond, Virginia for analysis and statisticalassessment.

The association between categorical variables and deliriumwere summarized using Cramer’s V scoring (See Figure 1).Cramer’s V is defined as the way of calculating correlation intables which have multiple rows and columns. After chi-squarehas determined significance, Cramer’s V is used to determinethe strength of association. We defined a strong relationship as aCramer’s V score over 0.25, a moderate relationship as a scorebetween 0.20 to 0.25, and a weak relationship below the score of0.20. The relationship between continuous variables and delir-ium were summarized using simple logistic regression. Multiplelogistic regression was used to obtain a complete picture of therisk associated with different treatments, controlling for clinicalvariables. Unless otherwise specified, all odds ratios reportedare adjusted according to this multiple logistic regression model.All analyses were performed in R 3.6.0.

Results

Of the various procedures evaluated, 104 patients had total hiparthroplasties (THA) (average age 62.9), 100 patients had above-knee amputation (AKA) (average age 71.4), 114 patients hadtotal knee arthroplasties (TKA) (average age 64.3), 96 patientshad below-knee amputation (BKA) (average age 68.7), and 26patients had trans-metatarsal amputation (TMA) (average age69.7). The demography of the patients in each group is summa-rized in Table 1.

Out of the 440 patients studied, 53 % of the patients hada nerve block procedure, either as a formal injection or inser-tion of a nerve catheter as postoperative pain management byan anesthesiologist after the procedure in the post-anaesthesiacare unit (PACU). Common types of nerve blocks used werefemoral nerve blocks, lateral femoral cutaneous nerve block andsciatic nerve blocks. The usual agents used for nerve block werebupivacaine or ropivacaine.

Among thirty different variables, age, length of stay andAmerican Society of Anesthesiologists (ASA) classification werecontinuous variables (Table 2). The average length of stay amongpatients with delirium was 11.5 days, and without delirium was6.3 days.

Nerve block, patient control anesthesia, oral narcotics, IVAcetaminophen, non-steroidal anti-inflammatory drugs and


gabapentin were utilized as main postoperative pain manage-ment strategies (Table 3).

Of the variables tested, their relationship with causing delir-ium are summarized below (Table 4a, 4b):

Age and dementia are associated with increased ratesof delirium, but psychiatric drug use and PTSD are not

We found that both age [OR = 1.05, 95% CI = (1.02, 1.08), P =0.0030] and dementia [OR = 4.60, 95% CI = (2.08, 10.10), P =0.0001] were positively associated with the likelihood of delir-ium. These results suggest that for each yearly increase in age,the odds of delirium increase by 1.05 and the odds of deliriumin patients with prior dementia is 4.60 times higher than thosewithout prior dementia. From the Cramer’s V figure, there wasalso a strong relation of the location of the discharge, diagnosisof PAD, and ASA score with the delirium. Patients with thediagnosis of CVA-TIA, CKD and CHF had a weaker associationwith postoperative delirium. Among the patients tested, we didnot find any association between prior psychiatric drug use anddelirium [OR = 0.88, 95% CI = (0.42, 1.75), P = 0.7248] or betweenPTSD and delirium [OR = 1.41, 95% CI = (0.57, 3.20), P = 0.4287].We also found a positive association between blood transfusion[OR = 2.67, 95% CI = (1.18, 6.16), P = 0.0207] and delirium (Table5).

Nerve block does not influence the odds of delirium

We tested whether the nerve block influences the incidence ofdelirium. We found that nerve block does not significantly in-crease the odds of delirium in patients [OR = 0.82, 95% CI =

(0.46, 1.47), P = 0.5126]. To test whether anaesthesia type has aninfluence on delirium we re-ran our multiple logistic regressionmodel controlling for anaesthesia-type (General, local, regional,spinal and epidural). We found that even after controlling foranesthesia there is still no association between nerve block anddelirium [OR = 0.78, 95% CI = (0.42, 1.42) P = 0.4149]. Addi-tionally, we tested whether anaesthesia types themselves haveany influence on delirium occurrences. The results show thatcompared to general anaesthesia, none of the treatment typeshad any significant relationship with delirium.

Gabapentin is associated with an increase in the oddsof delirium

To determine which medicines were associated with delirium,we tested five treatments (Acetaminophen IV, Gabapentin, peroral narcotics, patient-controlled anaesthesia, NSAIDs). Amongthe five, we found that only gabapentin [OR = 2.27, 95% CI= (1.24, 4.24), P = 0.0085] was associated with a difference indelirium levels. Based on these results, the odds of a patientwho was treated with gabapentin having delirium is 2.27 timeshigher than those without such treatment. Furthermore, we alsotested whether any particular interaction of drugs causes anincrease in delirium. We found no significant interactions.

Prior narcotic use and major events are associated withincreased odds of delirium

The odds of delirium was found to be significantly higher in pa-tients who had prior narcotics use than those who have not usednarcotics (OR = 2.34, 95% CI = 1.28, 4.27, P = 0.0053). Addition-ally, we find an increase in delirium among patients experiencingmajor events compared to those who did not (OR = 2.55, 95% CI= (1.01, 6.43), P = 0.0468).

Discussion

Delirium is a serious neurologic disorder that is characterized bydisturbances in one’s mental capabilities resulting in confusedthought processes, disorientation, memory loss and altered per-ception concerning one’s surroundings. While these aberrationsare commonly found in the delirious person, the range of pos-sibilities is plentiful as summarized in the accompanying Tableof the American Psychiatric Association’s Diagnostics and Sta-tistical Manual of Mental Disorders (DSM-5) in which deliriumis defined. The start of this condition is usually quite rapidand may manifest itself within hours or days following sometriggering event (See Table 6). [9]

Delirium is common in older patients and a frequent prob-lem in those requiring hospitalization.[10] Of note, it is the mostcommon surgical complication among older adults, with an inci-dence of some 15 to 25% after significant surgery overall and 50%after high-risk procedures such as hip fracture repair and cardiacsurgery.[10] In addition to age, the predisposing factors for thedevelopment of delirium are dementia, functional disabilities,and the high burden of coexisting diseases. Frequent precipi-tating factors include physical restraints, operative procedures,malnutrition, three or more medications (especially sedatives),use of a bladder catheter, and infection. [10],[11],[12] There areno definitive and specific medications that can prevent or allevi-ate delirium. Decreasing risk factors that trigger its developmentis presently the best prevention strategy.[10],[13]

As the population of the older age group has been increasing,the incidence of delirium has correspondingly increased along


with the associated cost burden of management.[14] There is nodoubt that postoperative delirium will significantly increase thecare due to prolonged length of hospital stay and the incrementalincrease in cost necessary to treat it.[15],[16] It is interesting tonote that delirium is projected to cost more than 48% of all daysin the hospital in patients 65 years or older.[16]

As an unintentional effect of hospitalization, delirium hasbeen one of the main cost-driving factors in healthcare. However,it has not been viewed with the same degree of importance asother cost issues in our hospital system. According to an analysisconducted in 2008, with cost adjustment for inflation, it wasreported that the cost of taking care of the delirious patient wasbetween $ 143 and $152 billion in one year.[16]

Delirium has both short- and long-term effects. The short-term effects are increased length of hospital stay, unanticipateddeath, need for institutional care at discharge, and often rehos-pitalization within 30 days. [17] Further, delirium can have anenormous impact on all individuals that are involved. Most

important is the patient, who may not know or understand whatis happening to him or herself, posing important safety issues.It may be a very emotional moment for the patient’s family andfriends to see their loved one not being able to understand themor relate to them appropriately. The delirious patient may alsodrain the energy and require more resources from the aspect ofnursing care. From a long-term standpoint, patients with delir-ium are often slow to improve or may not improve at all. Further,those patients who demonstrate no long-term improvement fre-quently require sustained institutional care from which theyeventually die. Even a brief period of postoperative deliriummay have long term effects on the ability to live independentlyafter that.[17][18]

Delirium is often unrecognized and underdiagnosed evenin the hospital setting. [19] Nurses are the primary source ofrecognition of any change in the patient’s physical and mentalstatus, but even they may miss the delirium when present. [20] Afurther issue is that the diagnosis of delirium has been somewhat


difficult because its precise diagnosis and definition occasionallyvaries between even delirium experts. [21]

The findings of the present study emphasize anew the impor-tance of delirium in the management of surgical patients andthe need for health care providers not to forget the ever-presentpossibility that this complication could arise. We found that theolder patients get, the more common delirium is in the postoper-ative setting. Thus, in anyone over 65 years of age, ever presentvigilance should be part of the surgeon’s and medical team’s ar-mamentarium not to miss this problem should it develop in thepostoperative period. We also found that in patients with priordementia, the odds of developing delirium is 4.6 times higherthan in those patients without prior dementia. Precisely whythis remains uncertain, but probably the neurologic derange-ments giving rise to dementia are somehow equally involvedin activating delirium. What role gender plays in subjecting apatient to the possibility of developing delirium cannot be an-swered from our study since most of the patients studied were

male without a large enough sample of females to derive anymeaningful comparisons.

Other factors linked to delirium in our study included patientdeposition at the time of discharge. Those requiring special careunits or skilled nursing homes frequently were the victims ofpostoperative delirium, which affected their ability to functionindependently, at least in the short term. We also found thatpatients with chronic peripheral artery disease (PAD), previouscerebral vascular accident (CVA-TIA), chronic kidney disease(CKD), and coronary artery disease (especially with chronicheart failure) also had a linkage with the development of post-operative delirium, although much less pronounced then inadvancing age or dementia. Since all these diseases involveproblems with arterial blood flow, it is not surprising that thiswould occur since presumably many of them also had brain per-fusion problems. Further, most of these patients had high ASAscores which we found linked to the possibility of developingdelirium. Also, of interest, the need for blood transfusion dur-


ing the various operations performed was linked with deliriumdevelopment. Conceivably this linkage was related to volumedepletion and/or inadequate arterial oxygenation, both of whichcould adversely affect brain function and result in delirium.

Interestingly, oral narcotics, patient-controlled anaesthesia,non-steroidal anti-inflammatory drugs, and intravenous Ac-etaminophen, all used to control postoperative pain, had noassociation with delirium development. Even the interactionof these drugs demonstrated no increase in delirium. In con-trast, gabapentin, when used for postoperative pain control, wasstrongly associated with delirium development. Presumably,the complex effects this drug has on neuro biochemistry aresomehow linked with delirium. Finally, prior narcotic use inpatients undergoing operations, resulted in a higher rate of delir-ium, again most likely because of changes in brain metabolism.Things not associated with increased rates of delirium in ourstudy included prior psychiatric drug use, post-traumatic stressdisorder, and the type of nerve block used for postoperative painmanagement. Further, regardless of the type of anaesthesia per-formed, there was still no association between the nerve blockperformed and delirium. Finally, no anesthetic treatment typeshad any relation with delirium.

Conclusions

In conclusion, as our population continues to live to older ages,it is virtually certain that delirium will be more common in oursurgical units and following operative procedures. Delirium willnot only increase the cost of patient care, but it will also leaveirreversible changes in the mental and physical activities of thepatient affected. It will likewise leave significant emotional scarsin the affected patient families. Taking care of delirious patientsis a huge challenge to healthcare providers as well. Going for-ward, awareness of delirium in any patient is vital. Patients whoare potential surgical candidates should be carefully screenedfor the possibility of delirium and steps taken as best as possi-ble to prevent this condition from occurring. When possible, itshould be identified early and managed appropriately. Usually,a multimodal approach is necessary to decrease the incidence ofdelirium.

Ethics approval and informed consent

Institutional Review Board, Richmond VA Medical Center. IRB#02373

Conflict of Interest

The authors have no conflict of interest in this study.


Funding

This study received no fund.

Author’s Contribution

All authors have: 1. Substantial contributions to conception anddesign, data acquisition, or data analysis and interpretation; 2.Drafting the article or critically revising it for important intellec-tual content; 3. Final approval of the version to be published;and 4. Agreement to be accountable for all aspects of the workin ensuring that questions related to the accuracy or integrity ofthe work are appropriately investigated and resolved.

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