Original Article
The association of gender and body mass index with postoperative pain scores when undergoing ankle fracture surgery Samuel Robert Grodofsky1, Ashish C Sinha1,2 Departments of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, 2Anesthesiology, Drexel University College of Medicine/ Hahnemann University Hospital, Philadelphia, Pennsylvania, USA 1
Abstract Background: Intraoperative administration of opiates for postoperative analgesia requires a dosing strategy without clear indicators of pain in an anesthetized patient. Preoperative patient characteristics such as body mass index (BMI), gender, age, and other patient characteristics may provide important information regarding opiate requirements. This study intends to determine if there is an association between gender or BMI and the immediate postoperative pain scores after undergoing an open reduction and internal fixation (ORIF) of an ankle fracture with general anesthesia and morphine only analgesia. Materials and Methods: Using a retrospective cohort design, the perioperative records were reviewed at a university healthcare hospital.One hundred and thirty-seven cases met all inclusion and no exclusion criteria. Postanesthesia care unit (PACU) records were reviewed for pain scores at first report and 30 min later as well as PACU opiate requirements. T-test, chi-square, and Mann-Whitney tests compared univariate data and multivariate analysis was performed by linear regression. Results: There were no statistically significant PACU pain score group differences based on gender or BMI. Post hoc analysis revealed that in the setting of similar pain scores, obese patients received a similar weight based intraoperative morphine dose when using adjusted body weight (ABW) compared to nonobese subjects. A further finding revealed a negative correlation between age and pain score (P = 0.001). Conclusion: This study did not find an association between obesity or gender and postoperative pain when receiving morphine only preemptive analgesia. This study does support the use of ABW as a means to calculate morphine dosing for obese patients and that age is associated with lower immediate pain scores. Key words: Acute pain, BMI, gender, morphine
Introduction The use of long acting opiates intraoperatively to blunt surgical stimulus and achieve postoperative analgesia proves challenging due to a highly variable pharmacological profile. While autonomic changes in an anesthetized patient provide some dosing feedback, using certain patient characteristics Address for correspondence: Dr. Samuel Robert Grodofsky, Department of Anesthesiology and Critical Care, Hospital University of Pennsylvania, 3400 Spruce Street, Dulles Building, 5th Floor, Philadelphia - 19104, Pennsylvania, USA. E-mail: [email protected] Access this article online Quick Response Code:
Website: www.joacp.org
DOI: 10.4103/0970-9185.130041
248
may assist in determining a safe, yet effective dose. There is evidence that suggests different pain processing based on gender and body mass index (BMI). For example, increased BMI and being the female gender have been demonstrated to act as independent risk factors for the development of chronic pain.[1-4] There is also copious experimental data investigating sex/gender differences in acute pain sensitivity through different mechanisms. When taking in the breadth of research in this subject, many reviews conclude that women have greater pain sensitivity,[5-7] but a recent meta-analysis accounting for poorly powered studies suggested that this pattern is not very clear or consistent.[8] There are a smaller number of published experimental models of pain investigating BMI as a variable with some evidence demonstrating that obese patients demonstrate a higher threshold for pain sensitivity.[9] Current clinical research into the use of systemic opiates for the treatment of postoperative acute pain suggests higher pain scores and greater narcotic requirements in women and patients with a higher BMI; however, these studies took a heterogeneous selection of surgical procedures.[10-12]
Journal of Anaesthesiology Clinical Pharmacology | April-June 2014 | Vol 30 | Issue 2
Grodofsky, et al.: The impact of gender and body mass index on postoperative pain
The present study is a retrospective cohort design to evaluate if there is an association between gender and/or BMI and reported postoperative pain scores after undergoing a similar surgical procedure — open reduction and internal fixation (ORIF) of an ankle fracture. The relevance of this study will be to assess whether two easily identifiable patient characteristics predict clinically significant differences in pain processing to factor into an intraoperative dosing strategy.
Materials and Methods The internal Institutional Review Board provided approval for the retrospective analysis of data using the electronic anesthesia medical record system (formerly DocuSys). A query to identify all patients undergoing an ORIF of the ankle between January 2006 and December 2011 was performed using the Current Procedural Terminology (CPT) codes 27814, 27822, and 27792. Inclusion criteria included patients undergoing general anesthesia and receiving morphine only for postoperative analgesia. The initial query yielded 179 cases. The patient’s perioperative electronic record was used to look for the following exclusion criteria: The use of regional (peripheral or neuraxial) anesthesia, the use of intraoperative hydromorphone, the use of more than 300 μg of fentanyl, the use of fentanyl less than 30 min prior to or upon emergence, or the use of fentanyl during transport to the post-anesthesia care unit (PACU), the administration of multimodal analgesia (e.g., ketamine, ketorolac), patients undergoing a repeat ORIF, American Society of Anesthesiologists physical status (ASA) 4 or E, remaining intubated after surgery, additional injuries requiring orthopedic intervention, use of total intravenous (IV) anesthesia, the preoperative presence of chronic pain requiring chronic opiate therapy. Five further cases were eliminated due to incomplete intraoperative or PACU documentation, leaving a total of 137 cases for analysis following study exclusion criteria. As cases were managed by autonomous anesthesia consultants, there was no standardization in technique, however after applying exclusion and inclusion criteria, cases conformed to the typical practices of induction and maintenance of general anesthesia practiced at our institution. Patients received premedication with midazolam IV (1-2 mg). Routine IV induction consisted of lidocaine 1-1.5 mg/kg, fentanyl 50-200 μg, propofol 1.5-2.5 mg/kg. The use of muscle relaxants varied among practitioners as there were some cases using succinylcholine, while most used nondepolarizing muscular blockers such as rocuronium, vecuronium, or cisatracurium. Intraoperative general anesthesia was maintained with volatile agents isoflurane, sevoflurane, or desflurane at a level of 0.8-1.5 minimum alveolar concentration
(MAC), to maintain acceptable hemodynamic variables. Ondansetron IV 4 mg was given upon closure and in most cases, neostigmine 0.07 mg/kg (max 5 mg) and glycopyrrolate 0.01 mg/kg (max 0.8 mg) were given to reverse residual neuromuscular blockade. In some cases nitrous oxide was used at the end of the cases during emergence. Cases that had variability from the described methods were reviewed by the study authors. No cases were excluded after chart review as it was determined that the different anesthetic technique would not likely influence reporting of pain scores in the PACU. The variable for analysis consisted of the patient’s PACU verbal numerical rating scores (NRS), which is rated on a subjective 0-10 point scale (0 = no pain, 10 = worst pain in life) upon first arrival and 30 min later. All patients were started on a morphine or hydromorphone patient controlled analgesia (PCA) in the PACU; however the total PCA dosing was not readily available in the electronic medical record. Supplemental opiates administered for breakthrough pain on top of the PCA were recorded in the PACU record and used for analysis. For non-morphine supplemental opiates provided in the PACU, a conversion of hydromorphone 1 mg: Morphine 7.7 mg and fentanyl 1 mg: Morphine 100 mg was used to establish morphine equivalents. Finally a weight based dose was calculated for total intraoperative morphine dosing by a total body weight (TBW) and then an adjusted body weight (ABW) based on ideal body weight (IBW). IBW is based on the Devine equation for IBW[13] and ABW using the equation ABW (kg) = IBW + 0.4 (TBW-IBW).[14] Based on the sample size, a P-value of 0.05 was considered to be significant. The data was analyzed using Statistical Package for Social Sciences (SPSS)® version 17.0 (SPSS Inc., Chicago IL). Univariate statistics were performed comparing males and females and patients with a BMI >30 kg/m2 to a BMI 30 kg/m2 received a smaller TBW calculated dose (P = 0.013), but a larger IBW calculated dose (P = 0.028). There was no significant difference between groups using the ABW calculation (P = 0.930).
5 (SD = 3.9) in the first report and 5 (SD = 3.4) after 30 min and received a mean dose of 3.4 mg (SD = 3.7) of morphine equivalents on top of the PCA in the PACU. Males reported a median pain NRS of 4 (SD = 3.8) in the first report and 5 (SD = 3.4) after 30 min and received a mean dose of 3.6 mg (SD = 5.6) of morphine equivalents on top of the PCA in the PACU. These differences were not statistically significant.
PACU scores: Figure 1 shows the differences in PACU NRS based on gender. Females reported a median pain NRS of
Figure 2 shows the differences in PACU NRS based on BMI greater than or less than 30 kg/m2. Patients with a BMI 30 kg/m2 reported a median pain NRS of 5 (SD = 4.0) in the first report and 5 (SD = 3.4) after 30 min and received a mean dose of 3.3 mg (SD = 5.3) of morphine equivalents on top of the PCA in the PACU. These
Figure 1: Box plot of the PACU pain NRS during first report (blue) and after 30 minutes (green) in males and females. The lines represent the median value with the shaded boxes representing interquartile range and whiskers representing total range
Figure 2: Box plot of the PACU pain NRS during first report (blue) and after 30 minutes (green) in Non-obese (BMI 30). The lines represent the median value with the shaded boxes representing interquartile range and whiskers representing total range
Regarding safety information, there were no recorded adverse events in the PACU that could be traced directly to opiate administration, such as respiratory arrest or naloxone administration. In addition, in no cases was naloxone administered at the end of the case by an anesthesia provider.
Table 1a: Male/female patient demographics and intraoperative morphine dosing Gender
N
Female Male
78 59
Mean age* BMI (kg/m2) Mean surgical Mean morphine Morphine dose Morphine dose by Morphine dose time (min) dose (mg)** by TBW (mg/kg) IBW (mg/kg)*** by ABW (mg/kg) 48.1 (16.5) 31.3 (7.5) 219 (91) 13.5 (5.2) 0.18 (0.09) 0.26 (0.13) 0.22 (0.11) 36.6 (13.1) 29.7 (6.5) 207 (64) 17.0 (5.2) 0.18 (0.07) 0.22 (0.07) 0.20 (0.07)
*P = 0.001, **P = 0.0003, ***P = 0.031
Table 1b: Obese/nonobese patient demographics and intraoperative morphine dosing BMI (kg/m2)
N
Mean age
30
76 61
41.3 (16.3) 45.5 (15.6)
Gender Mean (male) surgical time (min) 35 204 (60) 24 227 (100)
Mean morphine dose (mg)* 13.9 (4.7) 16.7 (6.0)
Morphine dose by TBW (mg/kg)** 0.20 (0.09) 0.16 (0.07)
Morphine Morphine dose by dose by ABW IBW (mg/kg)*** (mg/kg) 0.23 (0.10) 0.21 (0.09) 0.27 (0.12) 0.21 (0.09)
*P = 0.005, **P = 0.013, ***P = 0.028, BMI = Body mass index, ASA = American Society of Anesthesiologists physical status, TBW = Total body weight, IBW = Ideal body weight, ABW = Adjusted body weight
250
Journal of Anaesthesiology Clinical Pharmacology | April-June 2014 | Vol 30 | Issue 2
Grodofsky, et al.: The impact of gender and body mass index on postoperative pain
differences were not statistically significant and there was no significant linear relation of BMI and NRS. When looking at differences in changes in pain score from the first report to the report after 30 min, patients with a BMI 30 kg/m2 had an increase in NRS score by 0.51 (SD = 3.2), which is a trend to significance (P = 0.06). A linear regression analysis of age, BMI, gender, case length, and intraoperative morphine dose (based on TBW, IBW, and ABW) was performed and only age was found to have a significant independent correlation (Beta = −0.371, P = 0.001) during the first pain report. This correlation was not found to be significant after 30 min in the PACU. Taking into account that there was a statistical difference in age between males and females, a multivariate analysis adjusting for interaction between age and gender revealed no difference in NRS for the first reported pain score and 30 min pain score.
Discussion This study demonstrates no clinically significant differences in immediate postoperative pain scores or analgesic requirements between women and men and obese and nonobese patients when receiving general anesthesia with systemic morphine as the principal method of analgesia. A secondary finding in this analysis revealed a negative correlation between age and first reported pain score, which is consistent with the literature.[15,16] While this analysis is retrospective, it uses a database containing a uniform injury mechanism, surgical procedure and anesthetic approach. There is evidence in this analysis to support the pharmacokinetic adjustment of ABW to reflect lean body mass when dosing opiates in obese patients. Increased adiposity leads to physiologic changes that alter pharmacokinetics such as an increase in cardiac output, a disproportionate increase in adipose tissue relative to lean body weight (LBW) and other alterations that affect drug metabolism.[17] In addition, obese patients are not typically enrolled in clinical trials, a practice which limits the amount of data available for dosing parameters. Egan and colleagues demonstrated in computer simulations based on blood samples of obese and nonobese patients receiving an infusion of remifentanil that dosing based on measured LBW provides the optimal dosing scalar for obese patients.[18] Since measuring LBW is clinically impractical, the calculated approximations based on height and weight such as IBW or ABW is a more useful tool. According to our data, obese and nonobese patients received similar weight based dosing using the ABW calculation, while
not reporting any statistically significant difference of pain scores and the absence of any notable increased risk of adverse events. Since this is a post hoc analysis, this finding suggests further study into the use of ABW as a guide to intraoperative opiate dosing is needed. An unintended finding of this study is the negative correlation between pain scores and age. There are many factors that may contribute to this phenomenon such as psychosocial generational differences in pain processing, pharmacokinetic or pharmacodynamics changes with age or the residual effect of hypnotic agents from the surgery.[19] It is important to note that despite the age difference between men and women, this did not provide a significant confounding factor. The retrospective design, setting at a single hospital, study size, short follow-up, inability to calculate PACU PCA dose, and reliance on subjective pain scores are some of the limitations of this study. In addition, despite the inclusion of a morphine only analgesia, there is no standardization in the general anesthetic approach as the intraoperative dosing strategy that varies between anesthesia providers, whether there was a calculated weight based dose or one based on looking at physiologic parameters such as heart rate or ventilator rate that prevents standardization. The sample has been homogenized as much as possible by strict exclusion and inclusion criteria, however certain variabilities in consultant practices such as midazolam premedication, extubation criteria and use of nitrous oxide will impact the level of consciousness, and ability to provide an accurate immediate pain score in PACU. In addition, excess sedation will likely lead to more judicious opiate administration by PACU nurses and this cannot be controlled due to the absence of universal reporting in the medical record. Furthermore, there is no quantification of the severity of the ankle fractures that may serve as an important variable. In conclusion, this study provides analysis of clinical data to test the hypothesis that preoperative characteristics such as gender or BMI may correlate with immediate postoperative scores in the setting of a similar injury mechanism, surgery, and general anesthetic. While age is associated with slightly lower pain scores, there was no evidence that females or obese patients have clinically different responses.
References 1.
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Journal of Anaesthesiology Clinical Pharmacology | April-June 2014 | Vol 30 | Issue 2
McCarthy LH, Bigal ME, Katz M, Derby C, Lipton RB. Chronic pain and obesity in elderly people: Results from the Einstein ging study. J Am Geriatr Soc 2009;57:115-9. Hitt HC, McMillen RC, Thornton-Neaves T, Koch K, Cosby AG. Comorbidity of obesity and pain in a general population: Results from the southern pain prevalence study. J Pain 2007;8:430-6. 251
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Eriksen J, Jensen MK, Sjogren P, Ekholm O, Rasmussen NK. Epidemiology of chronic non-malignant pain in Denmark. Pain 2003;106:221-8. 4. Blyth FM, March LM, Brnabic AJ, Jorm LR, Williamson M, Cousins MJ. Chronic pain in Australia: A prevalence study. Pain 2001;89:127-34. 5. Fillingim RB, King CD, Ribeiro-Dasilva MC, Rahim-Williams B, Riley JL 3rd. Sex, gender, and pain: A review of recent clinical and experimental findings. J Pain 2009;10:447-85. 6. Mogil JS, Bailey AL. Sex and gender differences in pain and analgesia. Prog Brain Res 2010;186:141-57. 7. Fillingim RB, Ness TJ. Sex-related hormonal influences on pain and analgesic responses. Neurosci Biobehav Rev 2000;24: 485-501. 8. Racine M, Tousignant-Laflamme Y, Kloda LA, Dion D, Dupuis G, Choiniere M. A systematic literature review of 10 years of research on sex/gender and pain perception — Part 2: Do biopsychosocial factors alter pain sensitivity differently in women and men? Pain 2012;153:619-35. 9. Khimich S. Level of sensitivity of pain in patients with obesity. Acta Chir Hung 1997;36:166-7. 10. Aubrun F, Salvi N, Coriat P, Riou B. Sex- and age-related differences in morphine requirements for postoperative pain relief. Anesthesiology 2005;103:156-60. 11. Cepeda MS, Carr DB. Women experience more pain and require more morphine than men to achieve a similar degree of analgesia. Anesth Analg 2003;97:1464-8.
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12. Yen CR, Tsou MY, Mandell MS, Chan CT, Chan KH, Chen TH, et al. An analysis of patient variables that influence intravenous patientcontrolled analgesic use of morphine with quantile regression. Anesthesiology 2010;112:688-95. 13. Pai MP, Paloucek FP. The origin of the “ideal” body weight equations. Ann Pharmacother 2000;34:1066-9. 14. Lam TK, Leung DT. More on simplified calculation of body-surface area. N Engl J Med 1988;318:1130. 15. Gagliese L, Katz J. Age differences in postoperative pain are scale dependent: A comparison of measures of pain intensity and quality in younger and older surgical patients. Pain 2003;103:11-20. 16. Gibson SJ, Helme RD. Age-related differences in pain perception and report. Clin Geriatr Med 2001;17:433-56. 17. Ingrande J, Lemmens HJ. Dose adjustment of anaesthetics in the morbidly obese. Br J Anaesth 2010;105 Suppl 1:i16-23. 18. Egan TD, Huizinga B, Gupta SK, Jaarsma RL, Sperry RJ, Yee JB, et al. Remifentanil pharmacokinetics in obese versus lean patients. Anesthesiology 1998;89:562-73. 19. Minto CF, Schnider TW, Egan TD, Youngs E, Lemmens HJ, Gambus PL, et al. Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. I. Model development. Anesthesiology 1997;86:10-23. How to cite this article: Grodofsky SR, Sinha AC. The association of gender and body mass index with postoperative pain scores when undergoing ankle fracture surgery. J Anaesthesiol Clin Pharmacol 2014;30:248-52. Source of Support: Nil, Conflict of Interest: None declared.
Journal of Anaesthesiology Clinical Pharmacology | April-June 2014 | Vol 30 | Issue 2
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The association of gender and body mass index with postoperative pain scores when undergoing ankle fracture surgery Samuel Robert Grodofsky1, Ashish C Sinha1,2 Departments of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, 2Anesthesiology, Drexel University College of Medicine/ Hahnemann University Hospital, Philadelphia, Pennsylvania, USA 1
Abstract Background: Intraoperative administration of opiates for postoperative analgesia requires a dosing strategy without clear indicators of pain in an anesthetized patient. Preoperative patient characteristics such as body mass index (BMI), gender, age, and other patient characteristics may provide important information regarding opiate requirements. This study intends to determine if there is an association between gender or BMI and the immediate postoperative pain scores after undergoing an open reduction and internal fixation (ORIF) of an ankle fracture with general anesthesia and morphine only analgesia. Materials and Methods: Using a retrospective cohort design, the perioperative records were reviewed at a university healthcare hospital.One hundred and thirty-seven cases met all inclusion and no exclusion criteria. Postanesthesia care unit (PACU) records were reviewed for pain scores at first report and 30 min later as well as PACU opiate requirements. T-test, chi-square, and Mann-Whitney tests compared univariate data and multivariate analysis was performed by linear regression. Results: There were no statistically significant PACU pain score group differences based on gender or BMI. Post hoc analysis revealed that in the setting of similar pain scores, obese patients received a similar weight based intraoperative morphine dose when using adjusted body weight (ABW) compared to nonobese subjects. A further finding revealed a negative correlation between age and pain score (P = 0.001). Conclusion: This study did not find an association between obesity or gender and postoperative pain when receiving morphine only preemptive analgesia. This study does support the use of ABW as a means to calculate morphine dosing for obese patients and that age is associated with lower immediate pain scores. Key words: Acute pain, BMI, gender, morphine
Introduction The use of long acting opiates intraoperatively to blunt surgical stimulus and achieve postoperative analgesia proves challenging due to a highly variable pharmacological profile. While autonomic changes in an anesthetized patient provide some dosing feedback, using certain patient characteristics Address for correspondence: Dr. Samuel Robert Grodofsky, Department of Anesthesiology and Critical Care, Hospital University of Pennsylvania, 3400 Spruce Street, Dulles Building, 5th Floor, Philadelphia - 19104, Pennsylvania, USA. E-mail: [email protected] Access this article online Quick Response Code:
Website: www.joacp.org
DOI: 10.4103/0970-9185.130041
248
may assist in determining a safe, yet effective dose. There is evidence that suggests different pain processing based on gender and body mass index (BMI). For example, increased BMI and being the female gender have been demonstrated to act as independent risk factors for the development of chronic pain.[1-4] There is also copious experimental data investigating sex/gender differences in acute pain sensitivity through different mechanisms. When taking in the breadth of research in this subject, many reviews conclude that women have greater pain sensitivity,[5-7] but a recent meta-analysis accounting for poorly powered studies suggested that this pattern is not very clear or consistent.[8] There are a smaller number of published experimental models of pain investigating BMI as a variable with some evidence demonstrating that obese patients demonstrate a higher threshold for pain sensitivity.[9] Current clinical research into the use of systemic opiates for the treatment of postoperative acute pain suggests higher pain scores and greater narcotic requirements in women and patients with a higher BMI; however, these studies took a heterogeneous selection of surgical procedures.[10-12]
Journal of Anaesthesiology Clinical Pharmacology | April-June 2014 | Vol 30 | Issue 2
Grodofsky, et al.: The impact of gender and body mass index on postoperative pain
The present study is a retrospective cohort design to evaluate if there is an association between gender and/or BMI and reported postoperative pain scores after undergoing a similar surgical procedure — open reduction and internal fixation (ORIF) of an ankle fracture. The relevance of this study will be to assess whether two easily identifiable patient characteristics predict clinically significant differences in pain processing to factor into an intraoperative dosing strategy.
Materials and Methods The internal Institutional Review Board provided approval for the retrospective analysis of data using the electronic anesthesia medical record system (formerly DocuSys). A query to identify all patients undergoing an ORIF of the ankle between January 2006 and December 2011 was performed using the Current Procedural Terminology (CPT) codes 27814, 27822, and 27792. Inclusion criteria included patients undergoing general anesthesia and receiving morphine only for postoperative analgesia. The initial query yielded 179 cases. The patient’s perioperative electronic record was used to look for the following exclusion criteria: The use of regional (peripheral or neuraxial) anesthesia, the use of intraoperative hydromorphone, the use of more than 300 μg of fentanyl, the use of fentanyl less than 30 min prior to or upon emergence, or the use of fentanyl during transport to the post-anesthesia care unit (PACU), the administration of multimodal analgesia (e.g., ketamine, ketorolac), patients undergoing a repeat ORIF, American Society of Anesthesiologists physical status (ASA) 4 or E, remaining intubated after surgery, additional injuries requiring orthopedic intervention, use of total intravenous (IV) anesthesia, the preoperative presence of chronic pain requiring chronic opiate therapy. Five further cases were eliminated due to incomplete intraoperative or PACU documentation, leaving a total of 137 cases for analysis following study exclusion criteria. As cases were managed by autonomous anesthesia consultants, there was no standardization in technique, however after applying exclusion and inclusion criteria, cases conformed to the typical practices of induction and maintenance of general anesthesia practiced at our institution. Patients received premedication with midazolam IV (1-2 mg). Routine IV induction consisted of lidocaine 1-1.5 mg/kg, fentanyl 50-200 μg, propofol 1.5-2.5 mg/kg. The use of muscle relaxants varied among practitioners as there were some cases using succinylcholine, while most used nondepolarizing muscular blockers such as rocuronium, vecuronium, or cisatracurium. Intraoperative general anesthesia was maintained with volatile agents isoflurane, sevoflurane, or desflurane at a level of 0.8-1.5 minimum alveolar concentration
(MAC), to maintain acceptable hemodynamic variables. Ondansetron IV 4 mg was given upon closure and in most cases, neostigmine 0.07 mg/kg (max 5 mg) and glycopyrrolate 0.01 mg/kg (max 0.8 mg) were given to reverse residual neuromuscular blockade. In some cases nitrous oxide was used at the end of the cases during emergence. Cases that had variability from the described methods were reviewed by the study authors. No cases were excluded after chart review as it was determined that the different anesthetic technique would not likely influence reporting of pain scores in the PACU. The variable for analysis consisted of the patient’s PACU verbal numerical rating scores (NRS), which is rated on a subjective 0-10 point scale (0 = no pain, 10 = worst pain in life) upon first arrival and 30 min later. All patients were started on a morphine or hydromorphone patient controlled analgesia (PCA) in the PACU; however the total PCA dosing was not readily available in the electronic medical record. Supplemental opiates administered for breakthrough pain on top of the PCA were recorded in the PACU record and used for analysis. For non-morphine supplemental opiates provided in the PACU, a conversion of hydromorphone 1 mg: Morphine 7.7 mg and fentanyl 1 mg: Morphine 100 mg was used to establish morphine equivalents. Finally a weight based dose was calculated for total intraoperative morphine dosing by a total body weight (TBW) and then an adjusted body weight (ABW) based on ideal body weight (IBW). IBW is based on the Devine equation for IBW[13] and ABW using the equation ABW (kg) = IBW + 0.4 (TBW-IBW).[14] Based on the sample size, a P-value of 0.05 was considered to be significant. The data was analyzed using Statistical Package for Social Sciences (SPSS)® version 17.0 (SPSS Inc., Chicago IL). Univariate statistics were performed comparing males and females and patients with a BMI >30 kg/m2 to a BMI 30 kg/m2 received a smaller TBW calculated dose (P = 0.013), but a larger IBW calculated dose (P = 0.028). There was no significant difference between groups using the ABW calculation (P = 0.930).
5 (SD = 3.9) in the first report and 5 (SD = 3.4) after 30 min and received a mean dose of 3.4 mg (SD = 3.7) of morphine equivalents on top of the PCA in the PACU. Males reported a median pain NRS of 4 (SD = 3.8) in the first report and 5 (SD = 3.4) after 30 min and received a mean dose of 3.6 mg (SD = 5.6) of morphine equivalents on top of the PCA in the PACU. These differences were not statistically significant.
PACU scores: Figure 1 shows the differences in PACU NRS based on gender. Females reported a median pain NRS of
Figure 2 shows the differences in PACU NRS based on BMI greater than or less than 30 kg/m2. Patients with a BMI 30 kg/m2 reported a median pain NRS of 5 (SD = 4.0) in the first report and 5 (SD = 3.4) after 30 min and received a mean dose of 3.3 mg (SD = 5.3) of morphine equivalents on top of the PCA in the PACU. These
Figure 1: Box plot of the PACU pain NRS during first report (blue) and after 30 minutes (green) in males and females. The lines represent the median value with the shaded boxes representing interquartile range and whiskers representing total range
Figure 2: Box plot of the PACU pain NRS during first report (blue) and after 30 minutes (green) in Non-obese (BMI 30). The lines represent the median value with the shaded boxes representing interquartile range and whiskers representing total range
Regarding safety information, there were no recorded adverse events in the PACU that could be traced directly to opiate administration, such as respiratory arrest or naloxone administration. In addition, in no cases was naloxone administered at the end of the case by an anesthesia provider.
Table 1a: Male/female patient demographics and intraoperative morphine dosing Gender
N
Female Male
78 59
Mean age* BMI (kg/m2) Mean surgical Mean morphine Morphine dose Morphine dose by Morphine dose time (min) dose (mg)** by TBW (mg/kg) IBW (mg/kg)*** by ABW (mg/kg) 48.1 (16.5) 31.3 (7.5) 219 (91) 13.5 (5.2) 0.18 (0.09) 0.26 (0.13) 0.22 (0.11) 36.6 (13.1) 29.7 (6.5) 207 (64) 17.0 (5.2) 0.18 (0.07) 0.22 (0.07) 0.20 (0.07)
*P = 0.001, **P = 0.0003, ***P = 0.031
Table 1b: Obese/nonobese patient demographics and intraoperative morphine dosing BMI (kg/m2)
N
Mean age
30
76 61
41.3 (16.3) 45.5 (15.6)
Gender Mean (male) surgical time (min) 35 204 (60) 24 227 (100)
Mean morphine dose (mg)* 13.9 (4.7) 16.7 (6.0)
Morphine dose by TBW (mg/kg)** 0.20 (0.09) 0.16 (0.07)
Morphine Morphine dose by dose by ABW IBW (mg/kg)*** (mg/kg) 0.23 (0.10) 0.21 (0.09) 0.27 (0.12) 0.21 (0.09)
*P = 0.005, **P = 0.013, ***P = 0.028, BMI = Body mass index, ASA = American Society of Anesthesiologists physical status, TBW = Total body weight, IBW = Ideal body weight, ABW = Adjusted body weight
250
Journal of Anaesthesiology Clinical Pharmacology | April-June 2014 | Vol 30 | Issue 2
Grodofsky, et al.: The impact of gender and body mass index on postoperative pain
differences were not statistically significant and there was no significant linear relation of BMI and NRS. When looking at differences in changes in pain score from the first report to the report after 30 min, patients with a BMI 30 kg/m2 had an increase in NRS score by 0.51 (SD = 3.2), which is a trend to significance (P = 0.06). A linear regression analysis of age, BMI, gender, case length, and intraoperative morphine dose (based on TBW, IBW, and ABW) was performed and only age was found to have a significant independent correlation (Beta = −0.371, P = 0.001) during the first pain report. This correlation was not found to be significant after 30 min in the PACU. Taking into account that there was a statistical difference in age between males and females, a multivariate analysis adjusting for interaction between age and gender revealed no difference in NRS for the first reported pain score and 30 min pain score.
Discussion This study demonstrates no clinically significant differences in immediate postoperative pain scores or analgesic requirements between women and men and obese and nonobese patients when receiving general anesthesia with systemic morphine as the principal method of analgesia. A secondary finding in this analysis revealed a negative correlation between age and first reported pain score, which is consistent with the literature.[15,16] While this analysis is retrospective, it uses a database containing a uniform injury mechanism, surgical procedure and anesthetic approach. There is evidence in this analysis to support the pharmacokinetic adjustment of ABW to reflect lean body mass when dosing opiates in obese patients. Increased adiposity leads to physiologic changes that alter pharmacokinetics such as an increase in cardiac output, a disproportionate increase in adipose tissue relative to lean body weight (LBW) and other alterations that affect drug metabolism.[17] In addition, obese patients are not typically enrolled in clinical trials, a practice which limits the amount of data available for dosing parameters. Egan and colleagues demonstrated in computer simulations based on blood samples of obese and nonobese patients receiving an infusion of remifentanil that dosing based on measured LBW provides the optimal dosing scalar for obese patients.[18] Since measuring LBW is clinically impractical, the calculated approximations based on height and weight such as IBW or ABW is a more useful tool. According to our data, obese and nonobese patients received similar weight based dosing using the ABW calculation, while
not reporting any statistically significant difference of pain scores and the absence of any notable increased risk of adverse events. Since this is a post hoc analysis, this finding suggests further study into the use of ABW as a guide to intraoperative opiate dosing is needed. An unintended finding of this study is the negative correlation between pain scores and age. There are many factors that may contribute to this phenomenon such as psychosocial generational differences in pain processing, pharmacokinetic or pharmacodynamics changes with age or the residual effect of hypnotic agents from the surgery.[19] It is important to note that despite the age difference between men and women, this did not provide a significant confounding factor. The retrospective design, setting at a single hospital, study size, short follow-up, inability to calculate PACU PCA dose, and reliance on subjective pain scores are some of the limitations of this study. In addition, despite the inclusion of a morphine only analgesia, there is no standardization in the general anesthetic approach as the intraoperative dosing strategy that varies between anesthesia providers, whether there was a calculated weight based dose or one based on looking at physiologic parameters such as heart rate or ventilator rate that prevents standardization. The sample has been homogenized as much as possible by strict exclusion and inclusion criteria, however certain variabilities in consultant practices such as midazolam premedication, extubation criteria and use of nitrous oxide will impact the level of consciousness, and ability to provide an accurate immediate pain score in PACU. In addition, excess sedation will likely lead to more judicious opiate administration by PACU nurses and this cannot be controlled due to the absence of universal reporting in the medical record. Furthermore, there is no quantification of the severity of the ankle fractures that may serve as an important variable. In conclusion, this study provides analysis of clinical data to test the hypothesis that preoperative characteristics such as gender or BMI may correlate with immediate postoperative scores in the setting of a similar injury mechanism, surgery, and general anesthetic. While age is associated with slightly lower pain scores, there was no evidence that females or obese patients have clinically different responses.
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Journal of Anaesthesiology Clinical Pharmacology | April-June 2014 | Vol 30 | Issue 2
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