hypertensionandpostoperativepain:aprospective … · 2018. 10. 2. ·...

Research ArticleHypertension and Postoperative Pain: A ProspectiveObservational Study

Han-Liang Chiang ,1,2 Yu-Chi Huang,1 Huey-Shyan Lin,3 Min-Ho Chan,1,4

and Yuan-Yi Chia 1,2,4

1Department of Anesthesiology, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan2School of Medicine, National Defense Medicine Center, Taipei 114, Taiwan3School of Nursing, Fooyin University, Kaohsiung 831, Taiwan4School of Medicine, National Yang-Ming University, Taipei 112, Taiwan

Correspondence should be addressed to Yuan-Yi Chia; [email protected]

Received 2 October 2018; Revised 23 November 2018; Accepted 19 December 2018; Published 9 January 2019

Academic Editor: Yelena Granovsky

Copyright © 2019 Han-Liang Chiang et al. -is is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work isproperly cited.

Objectives. -e relationship between pain and hypertension is of great pathophysiological and clinical interest in the pain field, butthe mechanism is poorly understood. -is study used the postoperative patient-controlled analgesia (PCA) dose and the visualanalysis scale (VAS) score to assess the relationship between pain and hypertension.Methods. In this prospective study in a single-center hospital, 200 participants were enrolled and divided into three groups: normotensive group, hypertension withouttreatment group, and hypertension with treatment group. -e participants scheduled for elective inhalational general anesthesiawere interviewed at hospital admission. Results. A significant difference was observed in analgesic dosage on postoperative days 1,2, and 3 between the female normotensive group and female hypertension with treatment group (independent-samples, one-wayanalysis of covariance, age, and weight as covariates: P � 0.021, 0.014, 0.032). No significant differences in the VAS scores andPCA dosages were observed between the male normotensive group and any one of the male hypertensive groups. Conclusion. Weagree that hypertensive hypoanalgesia exists in some experimental settings. -e mechanism linking postoperative pain andhypertension is far more complex than we initially believed. -erefore, more studies are required to investigate the roles thatantihypertensive drugs, sex, and psychological stress play. Antihypertensive drugs may play a crucial role in mediating therelationship between pain and hypertension. Psychosocial factors were discussed but were not examined.

1. Introduction

Hypertension is a widespread problem around the world.-ere are few articles discussing about the relationshipbetween hypertension and postoperative acute pain. A studyon the relationship between hypertension and postoperativepain may offer clinical physicians guidance for pain man-agement in patients with hypertension. Hypertension haslong been associated with hypoalgesia [1]. Our previousstudy revealed the role of a β-blocker in anesthesia andpostoperative pain management after hysterectomy [2].Patients in an esmolol group used a lower quantity of PCAmorphine than those in a control group in the first 72

postoperative hours. Most studies discussing about re-lationship between postoperative pain and hypertensionhave not considered the interference of antihypertensivetreatment. -erefore, we designed a prospective observa-tional study comprising three groups (control, hypertensionwithout treatment, and hypertension with treatment) in asingle-center hospital to assess the relationship betweenhypertension and postoperative pain.

2. Materials and Methods

-e study protocol was approved by the hospital’s In-stitutional Review Board, and all subjects provided informed

HindawiPain Research and ManagementVolume 2019, Article ID 8946195, 6 pageshttps://doi.org/10.1155/2019/8946195

mailto:[email protected]://orcid.org/0000-0001-9342-9671http://orcid.org/0000-0003-3418-8008https://creativecommons.org/licenses/by/4.0/https://creativecommons.org/licenses/by/4.0/https://doi.org/10.1155/2019/8946195

consent prior to participation. -is manuscript adheres tothe applicable guidelines in the Consolidated Standards ofReporting Trials.

2.1. Design/Subjects. A prospective study was conducted inwhich potential subjects were identified through systematicreview of daily admission logs. Patients (aged 20 to 75 years)scheduled for elective general anesthesia and who werewilling to use morphine in postoperative pain control wereinterviewed at hospital admission. -e sample comprised200 participants who met the inclusion criteria.

2.1.1. Exclusion Criteria. Patients were excluded if they hadhad liver disease, renal disease, dementia, use of chronic painmedications, conscious disturbance, secondary hypertensionand myocardial infarction, cardiac bypass surgery, unstableangina, cerebrovascular events, congestive heart failure, orsignificant arrhythmia events in the preceding 6months.Pregnant or breastfeeding patients were also excluded.

Enrolled patients were divided into three groups asfollows:

(1) Normotensive group (control group)(2) Hypertension without treatment group(3) Hypertension with treatment group, described as

follows (according to the patient’s daily routinetreatment)

2.2. Assessment of Essential Hypertension History. Eligiblesubjects were informed that they were participating in astudy on essential hypertension and acute painmanagement.-e normotensive group was defined as not having a systolicpressure over 140mmHg or diastolic pressure over90mmHg more than twice between the admission andinterview. Patients who revealed that they had a history ofhypertension were enrolled in the essential hypertensiongroup. Patients who did not have a history of hypertensionbut who had a systolic pressure of over 140mmHg or adiastolic pressure of over 90mmHg more than twice be-tween admission and the interview were also placed in theessential hypertension group. Patients with hypertensionwere divided into two groups, a treatment group and anontreatment group, according to the use of antihyper-tensive agents. -e treatment and choice of drugs for hy-pertension were oriented to international guidelines by eachpatient’s clinician. -e treatment was divided into fourcategories: an angiotensin-converting-enzyme inhibitor(ACEI), a β-blocker, a calcium channel blocker, and adiuretic.

2.3. Induction of Anesthesia and Postoperative Pain 6erapy.General inhalation anesthesia was used and maintainedusing a standardized procedure by anesthesiologists. Nopremedication was administered to any of the patients.Before the surgery, we taught the patients how to use thePCA system and how to evaluate their own pain intensity byusing the visual analogue scale (0: no pain; 10: the worst pain

intensity). -e PCA system had the following initial settings:a bolus of 1mg of morphine at the patient’s demand,5minutes of lockout time, and an upper limit of 20mg ofmorphine. -e PCA dosage setting was adjusted dailydepending on the patient’s pain intensity at rest. A trainedresearch assistant obtained information on postoperativepain intensity, PCA consumption, and related side effectsfrom the medical records.

2.4. Measurement of Confounders. Information regardingdemographic, physiologic, anesthetic, and surgical con-founders was obtained using standardized questionnaires,the patients’ medical records, and physical examinations.-e heights and weights of the participants were obtainedfrom patient intake sheets. -e surgical sites were extractedfrom the operative reports approximately 1 week after ad-mission and were classified as one of the following: (1) upperabdominal, (2) lower abdominal, (3) urologic, (4) ortho-pedic, and (5) others. Type and duration of anesthesia wereextracted from the anesthetic record. Information regardingeach patient’s essential hypertension history, sex, age, pre-surgical weight, medical history, and postoperative coursewere collected. Furthermore, all nonopiate and opiate an-algesic use in the initial 72 postoperative hours was recorded.

2.5. Statistical Analysis. Independent-samples, one-wayanalysis of variance (ANOVA) and Tukey’s post hoc mul-tiple comparisons were used to test for significant differencesamong the three groups for continuous variables such as ageand body mass index (BMI) (Table 1). -e categoricalvariables, sex and American Society of AnesthesiologistsClassification (ASA Class), among the groups were de-termined using frequency distributions, and chi-square testswere performed to determine whether the distributionsdiffered significantly among the groups. Independent-samples, one-way analysis of covariance (ANCOVA) wasused to evaluate the relationship between hypertension or itstreatments and postoperative PCA consumption and painscores by sex, after adjusting for potential confounders. -ecovariates in independent-samples, one-way ANCOVAsdiffered significantly among the groups; the covariates weretaken from those variables that were determined to bepredictors as reported in the literature. Analyses wereperformed using SPSS (v. 22; IBM Corporation, Armonk,NY, USA). P< 0.05 was considered statistically significant.

3. Results

A total of 200 participants were recruited until December2015. -e first group of patients (patients without hyper-tension) comprised 52 subjects; the second group (patientswith hypertension without treatment) comprised 82 sub-jects; and the third group (patients with hypertension undermedical treatment) comprised 66 subjects. -e de-mographics of the patients are presented in Table 1.-e datawere separated by sex due to the differences in presentationin women and men (Tables 2 and 3, respectively). Withrespect to each sex, we adjusted for age and body weight

2 Pain Research and Management

Table 1: Demographic data for the three groups (N � 200).

Normotensive (N � 52) H/T without M (N � 82) H/T with M (N � 66) P valueAge (y/o) 49.2 ± 11.7†{ 56.8 ± 10.2‡ 61.2 ± 8.6

through independent-samples, one-way ANCOVA tocompare the VAS scores and morphine dosages among thethree groups. Significant differences were observed in an-algesics dosage on postoperative days 1, 2, and 3 in the threefemale groups (P � 0.021, 0.014, 0.032). A post hoc testrevealed a significant difference between the normotensivegroup and the hypertension under medication group. Sig-nificant differences were also observed in the postoperativepain scores of the male patients in terms of the analoguescales on movement (VASM) on postoperative day 1, theanalogue scales at rest (VASR) on postoperative day 1, andthe VASM on postoperative day 2 among the three groups(P � 0.015, 0.038, 0.032). -e results of the post hoc testrevealed no significant difference between the normotensivegroup and either of the hypertensive groups; however, asignificant difference was observed in the VASM and VASRon postoperative day 1 between the hypertension with andwithout treatment groups.

4. Discussion

-e relationship between hypertension and postoperativepain is of great pathophysiological and clinical interest in thepain field, but the mechanism is poorly understood [3].Hypertensive hypoanalgesia can be observed obviously in anexperimental setting [4]. It is a biological defensemechanismthat protects individuals from further harm through abaroreceptor that regulates the descending inhibitorypathways of pain that induce endogenous opioids [3]. Mostanimal and human studies have determined that hyper-tension is related to hypoanalgesia [5–7]. A study reportedan inverse relationship between resting blood pressure andacute pain sensitivity in healthy normotensives [8]. In ananimal model, a study showed that the expression ofgamma-aminobutyric acid receptors in nociceptive spinalneurons decreases during hypertension; another studyshowed caudal ventrolateral medullary reticular formationin nociceptive-cardiovascular integration [9, 10]. However,this mechanism is still debated because studies that haveused antiopioids have been unable to identify the cause ofhypertension-related hypoanalgesia [11–13]. Ring et al. useda double-blinded placebo control design and found that thedifferences in pain reporting between hypertension andnormotensive groups were unaffected by opioid blockadewith naltrexone. -eir results are congruent with those inmost opioid blockade studies [5] that have failed to supportthe hypothesis that hypertensive hypoalgesia is mediated byendogenous opioids. More research is required to clarify themechanism of hypertension-related hypoalgesia.

-is study determined that female patients with hy-pertension undergoing treatment required significantlymore morphine than did the normotensive patients duringthe initial 72 hours after operation. No differences inmorphine consumption and pain scores were observedbetween the normotensive group and either of the malehypertensive groups. An increasing number of studies haveused PCA dose to evaluate acute postoperative pain [14].France and Katz observed this relationship by using apatient-controlled analgesia (PCA) pump system in

response to an invasive procedure in prostate surgery [4].-ey reported that patients with hypertension had lowerpain scores than normotensive male patients who un-derwent radical prostatectomy. However, no differenceswere observed in PCA dosages, and they could not clearlyexplain the phenomenon [15]. In their discussion, theysuggested that morphine administration suppresses therelease of endogenous opiates previously activated in hy-pertension patients and that individuals with high bloodpressure require relatively high PCA dosages. -is sugges-tion is in agreement with our findings in which the femalepatients with hypertension used more PCA than the nor-motensive patients. In the same time, the hypertensionwithout medication group used more PCA dosages than thenormotensive group, but the difference was nonsignificant.Most studies have not included other factors that confoundthe relationship between postoperative pain and hyperten-sion. Our study introduced numerous covariates that mayhave interfered with the results, including sex, hypertensiontreatment, age, weight, and surgical duration.-e results didnot reveal direct evidence of the mechanism betweenpostoperative pain and hypertension, but we address im-portant key points that worth discussion. Human hyper-tension is complex and multifactorial, and distinguishingendocrine neurological components from genetic compo-nents is particularly difficult [16]. -erefore, the incidence ofhypoalgesia in individuals with a family history of hyper-tension is epidemiologic, but no causal evidence has beenpresented [16]. Most data are from Western studies andcannot be correlated with the hypoalgesia and hypertensiondata in routine use in clinical settings. Our data were derivedfrom only one Asian country (Taiwan), and after controllingfor many covariates, we realized that this topic is much morecomplex than we initially believed.

After comparing the differences in postoperative pain andsex reported in numerous studies, Zheng et al. found that ageand preoperative pain were major confounders for sex-baseddifferences in postoperative pain outcomes in a prospectivedatabase analysis. We therefore separated the data by sex foranalysis. Zheng et al. confirmed that female sex is a significantpredictor for postoperative pain after surgery, especially olderwomen (aged over 50 years). We assumed that because themean age of the female group (mean age: 55.5 years) was olderand some of the women may have been menopausal, morecomplex hormonal effects would have been present than inthemale group [17]. Because the female andmale patients hadcontrary presentations in our study, we observed no hyper-tensive hypoanalgesia effect in the male patients but observeda “reverse” hypertensive hypoanalgesia effect in the femalepatients [18]. -is finding is in agreement with the findings ofa 1999 study, in which sex-based differences in pain responsesto the cold pressor test in individuals with a positive ornegative parental history of hypertension were investigated[19, 20]. -e findings suggested that the generalizability of thehypoalgesic effects in women prone to hypertension should beinvestigated. On the other hand, hypertensive female withantihypertensive drugs use more morphine dosages thannormotensive female. -e antihypertensive drugs howeverimpacted the results among the female patients through an


unknown mechanism; moreover, the male patients withhypertension who did not use antihypertensive drugs re-ported more pain on postoperative day 1 than did those whouse antihypertensive drugs. In an animal study, mice treatedorally with several ACEIs or AT1RAs developed hypoalgesia;[21] however, more studies are required, particularly withantihypertensive drugs, to understand the mechanism [22].Palhares et al. reported a synergistic antinociceptive effectfrom a calcium channel blocker and a TRPV1 blocker in anacute pain model in mice [23]. In a human study, themechanisms acting through both antihypertensive and spe-cific pharmacodynamic properties may account for thenormalization of pain sensitivity observed in patients withhypertension during ACEI treatment. Physicians currentlyprescribe antihypertensive drugs by using several coreprinciples for treating hypertension, including a low dosageand combined therapy [24]. -ese core principles make itdifficult for studies like ours to define which categories ofantihypertensive drugs help patients control their hyperten-sion. We defined four categories of antihypertensive treat-ment at the beginning of this study, namely an ACEI, aβ-blocker, a calcium channel blocker, and a diuretic. We didnot have sufficient case numbers to analyze the subgroup inthe patients undergoing antihypertension treatment becausemost of our patients received multiple descriptions; futurestudies are required to confirm the findings of this study.

As already stated, morphine administration may suppressendogenous opiate release. We attempted to determine whywomen with hypertension use a larger morphine dose thannormotensive women. From a psychosocial aspect, pain notonly involves a central inhibitory mechanism but also anemotional element. In a review article [25], the authors ex-amined the relationship between psychosocial risk factors andhypertension. Sixteen of the studies reported an associationbetween psychosocial stressors and blood pressure anddemonstrated how the association plays a vital role in thedevelopment of hypertension. One 1993 study [26] reportedthat preoperative and postoperative emotional distress factorswere significantly related to the dose/demand ratio and hourlyanalgesic usage. Although we did not assess the psychosocialstress in our patients, according to the abovementionedhypothesis, female patients with hypertension have morepsychosocial stress than normotensive female patients andhave greater postoperative morphine requirements. -is isespecially true for patients treated using antihypertensivedrugs. Female patients with hypertension may require moreclinical observation during postoperative care, which can beprovided through multimodal pain treatment, includingperioperative psychological support [27].

4.1. Study Limitations

(1) We did not assess psychosocial stress in our patientsbefore and after the surgery

(2) We did not determine whether the patients (in thehypertension with treatment group) controlled theirhypertension properly using the prescriptions

(3) -is study did not conduct a double-blinded ex-periment; therefore, the patients might have knownthey were in dosage research and cause participantbias

(4) We did not have enough case numbers to assess therole of each type of antihypertensive drug

Data Availability

-e data used to support the findings of this study are in-cluded within the supplementary information file.

Disclosure

All authors have reviewed the original study data, reviewedthe data analysis, and approved the final paper, and allauthors are responsible for archiving the study files.

Conflicts of Interest

-e authors declare that they have no conflicts of interest.

Acknowledgments

-is study was supported by research grants (VGHKS 103and 104) from Kaohsiung Veterans General Hospital,Kaohsiung, Taiwan. -is manuscript was edited by WallaceAcademic Editing.

Supplementary Materials

Hypertension_pain.csv is our raw data that can be assessedfor public. (Supplementary Materials)

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hypertensionandpostoperativepain:aprospective … · 2018. 10. 2. ·...

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