- Email: [email protected]
Does femoral nerve analgesia impact the development of postoperative delirium in the elderly? A retrospective investigation
Acute Pain (2008) 10, 59—64
Does femoral nerve analgesia impact the development of postoperative delirium in the elderly? A retrospective investigation Elia Del Rosario ∗, Neus Esteve, Maria J. Sernandez, Carmen Batet, Jose L. Aguilar Department of Anesthesiology, Son Llatzer Hospital, Ctra Manacor km 4, CP 07198, Palma de Mallorca, Baleares, Spain Received 11 September 2007 ; received in revised form 24 January 2008; accepted 12 February 2008 Available online 1 April 2008 KEYWORDS Hip fracture; Femoral analgesia; Postoperative delirium
∗
Summary Background: The potential effects of femoral nerve analgesia on postoperative delirium and length of stay remains poorly investigated. After detecting several cases of delirium in postoperative patients, we sought to find out if femoral nerve analgesia would prove superior in the prevention of postoperative delirium when compared to a conventional analgesia regimen. Methods: Ninety-nine (99) patients were retrospectively investigated for delirium following hip fracture repair in 1 year (October 2004—October 2005). Patients were divided in two groups: Group 1 (n = 49) received patient-controlled femoral nerve analgesia (PCAF), Group 2 (n = 50) were treated with intravenous analgesia. All patients were studied for the following variables: age, gender, previous dementia, length of hospitalisation, blood transfusion, haemoglobin level at discharge, delirium, respiratory failure or oxygen therapy, heart failure or acute coronary disease, renal failure, stroke, rescue opioid analgesia, sitting and walking times, patients discharge to rehabilitation centre and patients discharge without walking recovery. Results: Patients in Group 1 showed significantly less occurrence of postoperative delirium than those treated with conventional analgesia (8.2% and 42%, respectively). Patients in PCAF group did not receive any morphine rescue medication in contrast to 28% of those of Group 2 (p < 0.001). Peripheral nerve analgesia substantially reduced the time when patients could first sit at their bedside (1.6 ± 0.6 and 2.0 ± 0.8, respectively). Conclusions: The incidence of postoperative delirium was lower in the PCAF group. The PCAF technique in hip fracture repair improves the quality of postoperative analgesia, without needing rescue opioid analgesia. © 2008 Elsevier B.V. All rights reserved.
Corresponding author. Tel.: +34 11 871202000; fax: +34 11 871202027. E-mail address: [email protected] (E. Del Rosario).
1366-0071/$ — see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.acpain.2008.02.001
60
1. Introduction Postoperative delirium occurs in 10—60% of patients [1]. The distinguishing features of this transient global disorder are impaired cognition, fluctuating levels of consciousness, altered psychomotor activity and a disturbed sleep—wake cycle. The incidence of hip fracture is increasing [2], most frequently in old patients. Postoperative pain after hip fracture repair surgery is a major concern. Postoperative patient-controlled femoral nerve analgesia (PCAF) facilitates early mobilisation and offers better pain control at movement than patientcontrolled intravenous opioid analgesia (PCIOA) [3]. Vaurio et al. [1] reported that postoperative pain and pain management strategies are independently associated with the development of postoperative delirium. The transient mental dysfunction can result in increased morbidity, delayed functional recovery, and prolonged hospital stay [4]. The adverse effects of postoperative delirium on health and health care costs make early diagnosis and prompt treatment imperative. A better choice would even be to prevent it. Since anaesthesiologists play an important role in the perioperative management of elderly patients undergoing surgery, it is imperative for them to have a good understanding of postoperative delirium. To reduce or prevent its occurrence, adequate perioperative analgesia regimen becomes important. Previous investigations [5] could not demonstrate differences between epidural analgesia and conventional IV opioid administration on the development of postoperative delirium. To date, the potential effects of PCAF after hip fracture repair on postoperative delirium and acute length of stay remains poorly investigated. The present retrospective investigation sought to find if PCAF would prove superior in the prevention of postoperative delirium and in early mobilisation after hip fracture repair, when compared to a conventional analgesia regimen.
2. Methods 2.1. Patient recruitment The medical records of a total of 99 patients were retrospectively investigated for the occurrence of delirium following surgery of hip fracture repair in 1 year (October 2004—October 2005). The inclusion criteria were consecutive patients, ≥50 years old who underwent hip fracture surgery with intradural anaesthesia. Patients were excluded if they have
E. Del Rosario et al. received general anaesthesia or epidural analgesia, presented failure of femoral analgesia, or had localised infection or coagulopathy.
2.2. Procedures Surgery was performed with a spinal anaesthetic using hyperbaric bupivacaine 0.5% (8—10 mg) in all patients. Patients were divided into two groups in terms of their postoperative pain management. Patients in Group 1 (n = 49) received a femoral catheter (PCAF) which remained in place for 48 h after surgery. Following a bolus dose of 30 ml bupivacaine 0.25%, the catheter was perfused with bupivacaine 0.1% at 5 ml/h. Patients were able to administer 5 ml bolus doses and the delivery pump was set at a 10-min lockout interval. Additionally, paracetamol (1 g/6 h) and metamizol (2 g/8 h) were given intravenously. Patients in Group 2 (n = 50) were treated conventionally with intravenous paracetamol and metamizol at the same doses aforementioned. Rescue medication was subcutaneous morphine 0.1 mg/kg or 5 mg if > 70 years old in both groups. Femoral nerve catheter placement was performed in the recovery room when motor block of the lower limb subsided (≤1 of the modified Bromage scale: 0 = no motor block; 1 = able to move knees; 2 = able to move feet only; 3 = unable to move feet). The initial stimulating needle entry point was located 1—1.5 cm lateral to the femoral artery pulsation just below the inguinal crease. After sterile preparation and draping, an insulated 19-gauge needle (StimulongPlus Plexus Catheter Set, Pajunk, Germany) was inserted and the femoral nerve was localised by eliciting quadriceps contractions at < 0.5 mA, with the peripheral nerve stimulator (Pajunk, Geisingen, Germany) set at 2 Hz and pulse width of 0.1 s. After localization of the femoral nerve, a 20-gauge stimulating nerve catheter was advanced 4—5 cm past the needle tip. After a negative aspiration test for blood, 30 ml of bupivacaine 0.25% was injected. We assessed by cold testing (alcohol-soaked swab) the cutaneous sensibility in the area of the femoral nerve to verify the correct position. Patients were instructed in the use of patient-controlled analgesia (PCA) pump (CADD-Legacy® PCA, Smiths, USA). After the initial bolus they received the femoral infusion.
2.3. Study parameters All patients were studied for the following variables: age, gender, previous dementia, length of hospitalisation, blood transfusion, haemoglobin level at discharge, delirium, respiratory failure or
Impact of femoral analgesia on delirium
61
oxygen therapy, heart failure or acute coronary disease, renal failure, stroke, rescue opioid analgesia, sitting and walking times, patients discharge to rehabilitation centre and patients discharge without walking recovery.
2.4. Assessment of delirium Following surgery, on any postoperative day or night of their hospital stay, patients were characterised as delirious if there was documentation in the medical or nursing record of altered mental status (confusion, disorientation, changes of level of consciousness, changes in the sleep—wake cycle). Delirium was classified in two degrees of severity, low or severe, according to the need of prescription of any antipsychotic drug (low grade: they do not need, severe: they need).
Fig. 1 Rate of delirium in the postoperative period, PCAF: femoral patient-controlled analgesia.
less than 0.05 was considered to indicate statistical significance.
3. Results
2.5. Statistical methods
3.1. Demographic, clinical data and events are described for both groups in Table 1
Data for the categorical variables are expressed as the number and the percentage of patients. For continuous variables, data are reported as estimated means ± S.D., and values were compared by unpaired Student’s t-tests after testing for normal distribution. Fisher’s exact test or a Chi-square test was used for categorical variables with nominal scales, and the Wilcoxon or Mann—Whitney ranksum test was used for those with ordinal scales. All statistical tests were two-tailed. A p-value of
Patients receiving multimodal pain treatment (PCAF) showed a relevant and significant lower occurrence of postoperative delirium than those treated with conventional analgesia (Fig. 1). Similarly, patients with a femoral catheter in place did not receive any morphine rescue medication in contrast to those treated conventionally (p < 0.001) (Fig. 2). Accordingly, peripheral nerve analgesia substantially reduced the time when patients could first sit at their bedside (p < 0.002). In contrast,
Table 1
Demographics, clinical dates, events PCAF: patient-controlled femoral nerve analgesia Group 1 PCAF (n = 49) n(%)/x ± S.D.
Group 2 (n = 50) n(%)/x ± S.D.
Sex (male) Age (years) Previous dementia Days of hospitalisation Time to seat (days) Time to walk (days) Haemoglobin at discharge (mg/dl) Blood transfusion Opioids rescue
10 (20.4) 81.5 ± 8.2 0 (0) 7.7 ± 3.0 1.6 ± 0.6 2.5 ± 1.3 9.8 ± 0.8 17 (34.7) 0 (0)
19 (38.0) 80.6 ± 9.5 1(0.5) 8.6 ± 3.5 2.0 ± 0.8 2.1 ± 1.7 10.0 ± 1.1 20 (40.0) 14 (28.0)
Agitation/delirium (any) No Low grade Severe grade
4 (8.2) 45 (91.8) 4 (8.2) 0 (0)
21 (42.0) 29 (58.0) 10 (20.0) 11 (22.0)
<0.001 <0.001
3 (6.1) 1 (2.0) 0 (0) 2 (4.1)
4 (8.0) 2 (4.0) 1 (2.0) 1 (2.0)
0.72 0.57 0.32 0.55
Complications (any) Respiratory failurea Heart diseaseb Renal disease S.D.: standard deviation. a Hypoxemia requiring oxygen therapy. b Including acute coronary syndrome.
p-Values 0.08 0.61 0.16 0.002 0.14 0.25 0.68 <0.001
62
Fig. 2 Need of rescue opioid analgesia, PCAF: femoral patient-controlled analgesia.
no statistical difference was found between groups with respect to when patients could first walk and concerning their overall hospital stay. There were no statistical differences (p > 0.05) in the transfusion index, haemoglobin level and rate of medical postoperative complications. Of all patients, 22.2% were discharged without walking (12% in PCAF group, 34% in group 2) and 19.1% of patients were discharged to a rehabilitation centre (4% in PCAF group, 24% in group 2). One year global mortality was 7%.
4. Discussion The results of the present investigation suggest a superiority of peripheral regional analgesia in the prevention of postoperative delirium. Patients with a femoral catheter in place receiving a multimodal analgesia regime displayed a better quality of postoperative analgesia showing no need for rescue medication. It has been demonstrated that opioid analgesic need in hip fracture is between 100 and 200 mcg/(kg day−1 ) of morphine in the first 4 postoperative days [6]. Additionally, due to the improved quality of pain relief in the PCAF group, patients recovered earlier as reflected by a shorter time to sit at the bedside. Although not reaching statistical difference, the time intervals to first walk and hospital stay were both shorter with multimodal pain treatment than in those patients receiving conventional pain therapy. The length of stay and the walking time depend not only on pain management strategies, but on the adoption of a multidisciplinary integrated care pathway [2]. Therefore it is difficult to demonstrate the impact of pain management strategies on the perioperative surgical outcomes, because many factors contribute to patients’ recovery. The reported incidence of postoperative acute confusional state or delirium varies widely and is common in older hospitalised patients. Particularly
E. Del Rosario et al. among elderly patients undergoing surgery, it is a frequent and serious clinical complication. The incidence in patients undergoing general surgery for all age groups ranges from 5% to 10% and for the elderly from 10% to 15% [7]. Reported rates in the hip surgery population vary from 5% to 61% [4,8]. Galanakis found an incidence of postoperative delirium of 40.5% in patients undergoing hip fracture surgery in contrast to only 14.7% in those of an elective hip joint replacement group [9]. This incidence of 40.5% is consistent with our finding of 42% in patients who received conventional postoperative therapy. Unfortunately, no detailed information of pain therapy is available in Galanakis’ investigation. The comparatively high incidence of delirium after surgery however contrasts substantially with the result in patients who received a multimodal pain treatment using a peripheral catheter technique. In the present study, only 4 (8.2%) of 49 individuals in this group showed symptoms of postoperative delirium. This raises the question if an improved analgesia leading to less disturbed sleep—wake cycles and an earlier mobilisation may be held responsible for this outcome. Very likely so, as patients in the multimodal pain treatment group were also able to sit at their bedside at an earlier time point than those in the conventional treatment group. Though the time to take their first walk was not much different between groups, a trend towards improved quality of analgesia with a multimodal regimen became visible. The mode of analgesia delivery is obviously an important consideration in managing postoperative pain. For acute postoperative pain control, current widely used methods involve IV or epidural modalities, with or without a patient-controlled device. Theoretically, similar to peripheral nerve analgesia as in the present investigation, epidurally administered analgesic medication should be associated with a decreased incidence of postoperative delirium. Mann et al. [5] did not find a significant difference between epidural and intravenous analgesia and the occurrence of postoperative delirium. However, the small number of available studies and study power (3—4%) limits the validity of this conclusion. Singelyn et al. [10] and Capdevila et al. [11] studies found that in contrast to epidural analgesia regional analgesic techniques improve early rehabilitation after major knee surgery by effectively controlling pain during continuous passive motion, thereby hastening convalescence. Side effects were encountered more frequently in the continuous epidural infusion group. Syngelin et al. also demonstrated that, after total hip arthroplasty, femoral
Impact of femoral analgesia on delirium nerve block provides analgesia comparable to epidural analgesia, but induces fewer side effects or complications [12]. It has been suggested that the analgesic effect of this technique is due to the cephalic spread of the local anesthetic inside the psoas compartment, reaching the lumbar plexus [13]. Nevertheless, in our opinion, it is necessary to use a multimodal approach to ensure the success of the analgesia. Baseline medication in the present study consisted of analgesics known to induce delirium in the elderly either to only a minimal degree or not at all. Previous investigations have shown that in postoperative pain treatment following knee or hip arthroplasty, fentanyl was almost equal to morphine on pain relief with a 10% lower occurrence rate of delirium [14]. In contrast, hydromorphone [15] and particularly meperidine [16] showed a substantial frequency of delirium in the postoperative time period. The 3-glucuronide metabolites of both morphine and hydromorphone can lead to neuroexcitation, whereas fentanyl undergoes hepatic biotransformation to inactive metabolites. Morphine also undergoes hepatic conjugation to form morphine 6glucuronide, an opioid agonist. Although some studies have examined the relative analgesic efficacy and adverse effects profile of morphine compared to morphine 6-glucuronide, none has evaluated their impact on postoperative delirium. In how far rescue medication of morphine given to patients treated with conventional analgesics contributed to the higher occurrence of delirium in the presented study remains speculative but this aspect cannot be excluded. Still, the fact that there is a remote chance that morphine and many other opioids may lead to a higher occurrence of delirium justifies a regional analgesic technique and as demonstrated in the present investigation preferably a peripheral one.
4.1. Limitations of this study Patients were classified as having developed delirium if there was documentation of altered mental status either in the medical record or in the nursing record. We did not use screening tools to identify cognitive disorders as confusion assessment method [17]. It is a recognised tool but it is a punctual measurement. Therefore we also compiled the alterations undergone during the night, when episodes of delirium are more frequent. Using screening tools allows us potentially to diagnose cognitive disturbance without agitation. Probably this kind of disturbances does not impact on surgery outputs. Other weakness of the study could be that we did not assess pain by Numeric Scale or Visual Analogic
63 Scale. We used an indirect method, as consumption of opioids. The retrospective nature of our study did not allow us to have this data. The average age of our patients was 81 years old, which makes VAS assessment difficult or impossible in many cases. Elderly patients with delirium might not effectively communicate VAS score. Pain evaluation might be inaccurate in elderly patients with pre-existing cognitive dysfunction or cultural barriers, and thus in turn might lead to inappropriate analgesic dosing or to confuse pain with delirium. Demonstrated risk factors of delirium are gender, previous dementia and general anaesthesia [4]. We did not exclude patients with previous dementia or with previous use of antipsychotic drugs, what could be a methodological flaw, but we only found one case of Alzheimer disease in Group 2 (NO femoral). Patients age, previous ambulatory and living status, previous dependence in basic and instrumental activities of daily living, medical comorbidities, and fracture type did not influence the appearance of delirium. There are many other factors that could impact in the development of cognitive disturbances but they have not been studied, such as time between fracture and surgery, duration of surgery, previously use of antipsychotic drugs and drug interactions. In conclusion, it appears that a combination of a local anaesthetic administered by means of a femoral catheter and intravenous paracetamol and metamizol could be superior to a conventional pain treatment consisting only of the two latter drugs. Patients treated conventionally required significantly more rescue morphine analgesia than did those receiving a multimodal (femoral catheter + IV paracetamol/metamizol) therapy. Additionally, opioids themselves carry a higher or lower risk of producing delirium depending on their metabolite profile. It remains to be seen if future studies on peripheral nerve analgesia can confirm the present results of reduction of postoperative delirium a postoperative complication frequently seen in the elderly patient population.
References [1] Vaurio LE, Sands LP, Wang Y, Mullen EA, Leung JM. Postoperative delirium: the importance of pain and pain management. Anesth Analg 2006;102:1267—73. [2] Gholve PA, Kosygan KP, Sturdee SW, Faraj AA. Mutidisciplinary integrated care pathway for fractured neck of femur. A prospective trial with improved outcome. Injury 2005;36:93—8. ¨ [3] Tuncer S, Sert OA, Yosunkaya A, Mutlu M, C ¸ elic J, Okesli S. Patient controlled femoral nerve analgesia vs PCAIV for postoperative analgesia alter trochanteric fracture repair. Acute Pain 2003;4:105—8.
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[4] Edelstein DM, Aharonoff GB, Karp A, Capla EL, Zuckerman JD, Koval J. Effect of postoperative delirium on outcome after hip fractured. Clin Orthop Relat Res 2004;422:195—200. [5] Mann C, Pouzeratte Y, Boccara G, Peccoux C, Vergne C, Brunat G, et al. Comparison of intravenous or epidural patient-controlled analgesia in the elderly after major abdominal surgery. Anesthesiology 2000;92:433—41. [6] Bang FN, Tange KM, Bjarne KB, Pia Soe JP, Henrik K. Effect of postoperative epidural analgesia on rehabilitation and pain after hip fracture surgery: a randomized, double-blind placebo-controlled trial. Anesthesiology 2005;102(6):1197—204. [7] Litaker D, Locala J, Franco K, Bronson DL, Tannous Z. Preoperative risk factors for postoperative delirium. Gen Hosp Psychiatry 2001;23:84—9. [8] Gustafson Y, Brannstrom B, Berggren D. A geriatric— anesthesiologic program to reduce acute confusional states in elderly patients treated for femoral neck fractures. J Am Geriatr Soc 1991;39:655—62. [9] Galanakis P, Bickel H, Gradinger R, Gradinger R, Von Gumppenberg S, Forstl H. Acute confusional state in the elderly following hip surgery: incidence, risk factors and complications. Int J Geriatr Psychiatry 2001;16: 349—55. [10] Singelyn FJ, Pendeville E, Gouverneur JM. Effects of PCAIV with morphine, continuous epidural analgesia, and continuous 3-1 block on postoperative pain after total knee arthroplasty. Anesth Analg 1998;87:88—92.
[11] Capdevila X, Barthelet Y, Biboulet P, Ryckwaert Y, Rubenovitch J, d’Athis F. Effects of perioperative analgesic technique on the surgical outcome and duration of rehabilitation after major knee surgery. Anesthesiology 1999;91:8—15. [12] Singelyn F, Gouverneur JM. Postoperative analgesia alter total hip arthroplasty: IV PCA with morphine, patientcontrolled epidural analgesia, or continuous ‘‘3-in-1’’ block: a prospective evaluation by our acute pain service in more than 1300 patients. J Clin Anesth 1999;11:550—4. [13] Singelyn FJ, Vanderelst PE, Gouverneur JM. Extended femoral nerve sheath block after total hip arthroplasty: continuous versus patient-controlled techniques. Anesth Analg 2001;92(2):455—9. [14] Herrick IA, Ganapathy S, Komar W, Kirkby J, Moote CA, Dobkowski W, et al. Postoperative cognitive impairment in the elderly: choice of patient-controlled analgesia opioid. Anaesthesia 1996;51:356—60. [15] Rapp SE, Egan KJ, Ross BK, Wild LM, Terman GW, Ching JM. A multidimensional comparison of morphine and hydromorphone patient-controlled analgesia. Anesth Analg 1996;82:1043—8. [16] Marcantonio ER, Juarez G, Goldman L, Mangione CM, Ludwig LE, Lind L, et al. The relationship of postoperative delirium with psychoactive medications. JAMA 1994;272:1518—22. [17] Inouye S, van Dycke C, Alessi C, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: the confusion assessment method. Ann Intern Med 1990;113:941—8.
Available online at www.sciencedirect.com
Does femoral nerve analgesia impact the development of postoperative delirium in the elderly? A retrospective investigation Elia Del Rosario ∗, Neus Esteve, Maria J. Sernandez, Carmen Batet, Jose L. Aguilar Department of Anesthesiology, Son Llatzer Hospital, Ctra Manacor km 4, CP 07198, Palma de Mallorca, Baleares, Spain Received 11 September 2007 ; received in revised form 24 January 2008; accepted 12 February 2008 Available online 1 April 2008 KEYWORDS Hip fracture; Femoral analgesia; Postoperative delirium
∗
Summary Background: The potential effects of femoral nerve analgesia on postoperative delirium and length of stay remains poorly investigated. After detecting several cases of delirium in postoperative patients, we sought to find out if femoral nerve analgesia would prove superior in the prevention of postoperative delirium when compared to a conventional analgesia regimen. Methods: Ninety-nine (99) patients were retrospectively investigated for delirium following hip fracture repair in 1 year (October 2004—October 2005). Patients were divided in two groups: Group 1 (n = 49) received patient-controlled femoral nerve analgesia (PCAF), Group 2 (n = 50) were treated with intravenous analgesia. All patients were studied for the following variables: age, gender, previous dementia, length of hospitalisation, blood transfusion, haemoglobin level at discharge, delirium, respiratory failure or oxygen therapy, heart failure or acute coronary disease, renal failure, stroke, rescue opioid analgesia, sitting and walking times, patients discharge to rehabilitation centre and patients discharge without walking recovery. Results: Patients in Group 1 showed significantly less occurrence of postoperative delirium than those treated with conventional analgesia (8.2% and 42%, respectively). Patients in PCAF group did not receive any morphine rescue medication in contrast to 28% of those of Group 2 (p < 0.001). Peripheral nerve analgesia substantially reduced the time when patients could first sit at their bedside (1.6 ± 0.6 and 2.0 ± 0.8, respectively). Conclusions: The incidence of postoperative delirium was lower in the PCAF group. The PCAF technique in hip fracture repair improves the quality of postoperative analgesia, without needing rescue opioid analgesia. © 2008 Elsevier B.V. All rights reserved.
Corresponding author. Tel.: +34 11 871202000; fax: +34 11 871202027. E-mail address: [email protected] (E. Del Rosario).
1366-0071/$ — see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.acpain.2008.02.001
60
1. Introduction Postoperative delirium occurs in 10—60% of patients [1]. The distinguishing features of this transient global disorder are impaired cognition, fluctuating levels of consciousness, altered psychomotor activity and a disturbed sleep—wake cycle. The incidence of hip fracture is increasing [2], most frequently in old patients. Postoperative pain after hip fracture repair surgery is a major concern. Postoperative patient-controlled femoral nerve analgesia (PCAF) facilitates early mobilisation and offers better pain control at movement than patientcontrolled intravenous opioid analgesia (PCIOA) [3]. Vaurio et al. [1] reported that postoperative pain and pain management strategies are independently associated with the development of postoperative delirium. The transient mental dysfunction can result in increased morbidity, delayed functional recovery, and prolonged hospital stay [4]. The adverse effects of postoperative delirium on health and health care costs make early diagnosis and prompt treatment imperative. A better choice would even be to prevent it. Since anaesthesiologists play an important role in the perioperative management of elderly patients undergoing surgery, it is imperative for them to have a good understanding of postoperative delirium. To reduce or prevent its occurrence, adequate perioperative analgesia regimen becomes important. Previous investigations [5] could not demonstrate differences between epidural analgesia and conventional IV opioid administration on the development of postoperative delirium. To date, the potential effects of PCAF after hip fracture repair on postoperative delirium and acute length of stay remains poorly investigated. The present retrospective investigation sought to find if PCAF would prove superior in the prevention of postoperative delirium and in early mobilisation after hip fracture repair, when compared to a conventional analgesia regimen.
2. Methods 2.1. Patient recruitment The medical records of a total of 99 patients were retrospectively investigated for the occurrence of delirium following surgery of hip fracture repair in 1 year (October 2004—October 2005). The inclusion criteria were consecutive patients, ≥50 years old who underwent hip fracture surgery with intradural anaesthesia. Patients were excluded if they have
E. Del Rosario et al. received general anaesthesia or epidural analgesia, presented failure of femoral analgesia, or had localised infection or coagulopathy.
2.2. Procedures Surgery was performed with a spinal anaesthetic using hyperbaric bupivacaine 0.5% (8—10 mg) in all patients. Patients were divided into two groups in terms of their postoperative pain management. Patients in Group 1 (n = 49) received a femoral catheter (PCAF) which remained in place for 48 h after surgery. Following a bolus dose of 30 ml bupivacaine 0.25%, the catheter was perfused with bupivacaine 0.1% at 5 ml/h. Patients were able to administer 5 ml bolus doses and the delivery pump was set at a 10-min lockout interval. Additionally, paracetamol (1 g/6 h) and metamizol (2 g/8 h) were given intravenously. Patients in Group 2 (n = 50) were treated conventionally with intravenous paracetamol and metamizol at the same doses aforementioned. Rescue medication was subcutaneous morphine 0.1 mg/kg or 5 mg if > 70 years old in both groups. Femoral nerve catheter placement was performed in the recovery room when motor block of the lower limb subsided (≤1 of the modified Bromage scale: 0 = no motor block; 1 = able to move knees; 2 = able to move feet only; 3 = unable to move feet). The initial stimulating needle entry point was located 1—1.5 cm lateral to the femoral artery pulsation just below the inguinal crease. After sterile preparation and draping, an insulated 19-gauge needle (StimulongPlus Plexus Catheter Set, Pajunk, Germany) was inserted and the femoral nerve was localised by eliciting quadriceps contractions at < 0.5 mA, with the peripheral nerve stimulator (Pajunk, Geisingen, Germany) set at 2 Hz and pulse width of 0.1 s. After localization of the femoral nerve, a 20-gauge stimulating nerve catheter was advanced 4—5 cm past the needle tip. After a negative aspiration test for blood, 30 ml of bupivacaine 0.25% was injected. We assessed by cold testing (alcohol-soaked swab) the cutaneous sensibility in the area of the femoral nerve to verify the correct position. Patients were instructed in the use of patient-controlled analgesia (PCA) pump (CADD-Legacy® PCA, Smiths, USA). After the initial bolus they received the femoral infusion.
2.3. Study parameters All patients were studied for the following variables: age, gender, previous dementia, length of hospitalisation, blood transfusion, haemoglobin level at discharge, delirium, respiratory failure or
Impact of femoral analgesia on delirium
61
oxygen therapy, heart failure or acute coronary disease, renal failure, stroke, rescue opioid analgesia, sitting and walking times, patients discharge to rehabilitation centre and patients discharge without walking recovery.
2.4. Assessment of delirium Following surgery, on any postoperative day or night of their hospital stay, patients were characterised as delirious if there was documentation in the medical or nursing record of altered mental status (confusion, disorientation, changes of level of consciousness, changes in the sleep—wake cycle). Delirium was classified in two degrees of severity, low or severe, according to the need of prescription of any antipsychotic drug (low grade: they do not need, severe: they need).
Fig. 1 Rate of delirium in the postoperative period, PCAF: femoral patient-controlled analgesia.
less than 0.05 was considered to indicate statistical significance.
3. Results
2.5. Statistical methods
3.1. Demographic, clinical data and events are described for both groups in Table 1
Data for the categorical variables are expressed as the number and the percentage of patients. For continuous variables, data are reported as estimated means ± S.D., and values were compared by unpaired Student’s t-tests after testing for normal distribution. Fisher’s exact test or a Chi-square test was used for categorical variables with nominal scales, and the Wilcoxon or Mann—Whitney ranksum test was used for those with ordinal scales. All statistical tests were two-tailed. A p-value of
Patients receiving multimodal pain treatment (PCAF) showed a relevant and significant lower occurrence of postoperative delirium than those treated with conventional analgesia (Fig. 1). Similarly, patients with a femoral catheter in place did not receive any morphine rescue medication in contrast to those treated conventionally (p < 0.001) (Fig. 2). Accordingly, peripheral nerve analgesia substantially reduced the time when patients could first sit at their bedside (p < 0.002). In contrast,
Table 1
Demographics, clinical dates, events PCAF: patient-controlled femoral nerve analgesia Group 1 PCAF (n = 49) n(%)/x ± S.D.
Group 2 (n = 50) n(%)/x ± S.D.
Sex (male) Age (years) Previous dementia Days of hospitalisation Time to seat (days) Time to walk (days) Haemoglobin at discharge (mg/dl) Blood transfusion Opioids rescue
10 (20.4) 81.5 ± 8.2 0 (0) 7.7 ± 3.0 1.6 ± 0.6 2.5 ± 1.3 9.8 ± 0.8 17 (34.7) 0 (0)
19 (38.0) 80.6 ± 9.5 1(0.5) 8.6 ± 3.5 2.0 ± 0.8 2.1 ± 1.7 10.0 ± 1.1 20 (40.0) 14 (28.0)
Agitation/delirium (any) No Low grade Severe grade
4 (8.2) 45 (91.8) 4 (8.2) 0 (0)
21 (42.0) 29 (58.0) 10 (20.0) 11 (22.0)
<0.001 <0.001
3 (6.1) 1 (2.0) 0 (0) 2 (4.1)
4 (8.0) 2 (4.0) 1 (2.0) 1 (2.0)
0.72 0.57 0.32 0.55
Complications (any) Respiratory failurea Heart diseaseb Renal disease S.D.: standard deviation. a Hypoxemia requiring oxygen therapy. b Including acute coronary syndrome.
p-Values 0.08 0.61 0.16 0.002 0.14 0.25 0.68 <0.001
62
Fig. 2 Need of rescue opioid analgesia, PCAF: femoral patient-controlled analgesia.
no statistical difference was found between groups with respect to when patients could first walk and concerning their overall hospital stay. There were no statistical differences (p > 0.05) in the transfusion index, haemoglobin level and rate of medical postoperative complications. Of all patients, 22.2% were discharged without walking (12% in PCAF group, 34% in group 2) and 19.1% of patients were discharged to a rehabilitation centre (4% in PCAF group, 24% in group 2). One year global mortality was 7%.
4. Discussion The results of the present investigation suggest a superiority of peripheral regional analgesia in the prevention of postoperative delirium. Patients with a femoral catheter in place receiving a multimodal analgesia regime displayed a better quality of postoperative analgesia showing no need for rescue medication. It has been demonstrated that opioid analgesic need in hip fracture is between 100 and 200 mcg/(kg day−1 ) of morphine in the first 4 postoperative days [6]. Additionally, due to the improved quality of pain relief in the PCAF group, patients recovered earlier as reflected by a shorter time to sit at the bedside. Although not reaching statistical difference, the time intervals to first walk and hospital stay were both shorter with multimodal pain treatment than in those patients receiving conventional pain therapy. The length of stay and the walking time depend not only on pain management strategies, but on the adoption of a multidisciplinary integrated care pathway [2]. Therefore it is difficult to demonstrate the impact of pain management strategies on the perioperative surgical outcomes, because many factors contribute to patients’ recovery. The reported incidence of postoperative acute confusional state or delirium varies widely and is common in older hospitalised patients. Particularly
E. Del Rosario et al. among elderly patients undergoing surgery, it is a frequent and serious clinical complication. The incidence in patients undergoing general surgery for all age groups ranges from 5% to 10% and for the elderly from 10% to 15% [7]. Reported rates in the hip surgery population vary from 5% to 61% [4,8]. Galanakis found an incidence of postoperative delirium of 40.5% in patients undergoing hip fracture surgery in contrast to only 14.7% in those of an elective hip joint replacement group [9]. This incidence of 40.5% is consistent with our finding of 42% in patients who received conventional postoperative therapy. Unfortunately, no detailed information of pain therapy is available in Galanakis’ investigation. The comparatively high incidence of delirium after surgery however contrasts substantially with the result in patients who received a multimodal pain treatment using a peripheral catheter technique. In the present study, only 4 (8.2%) of 49 individuals in this group showed symptoms of postoperative delirium. This raises the question if an improved analgesia leading to less disturbed sleep—wake cycles and an earlier mobilisation may be held responsible for this outcome. Very likely so, as patients in the multimodal pain treatment group were also able to sit at their bedside at an earlier time point than those in the conventional treatment group. Though the time to take their first walk was not much different between groups, a trend towards improved quality of analgesia with a multimodal regimen became visible. The mode of analgesia delivery is obviously an important consideration in managing postoperative pain. For acute postoperative pain control, current widely used methods involve IV or epidural modalities, with or without a patient-controlled device. Theoretically, similar to peripheral nerve analgesia as in the present investigation, epidurally administered analgesic medication should be associated with a decreased incidence of postoperative delirium. Mann et al. [5] did not find a significant difference between epidural and intravenous analgesia and the occurrence of postoperative delirium. However, the small number of available studies and study power (3—4%) limits the validity of this conclusion. Singelyn et al. [10] and Capdevila et al. [11] studies found that in contrast to epidural analgesia regional analgesic techniques improve early rehabilitation after major knee surgery by effectively controlling pain during continuous passive motion, thereby hastening convalescence. Side effects were encountered more frequently in the continuous epidural infusion group. Syngelin et al. also demonstrated that, after total hip arthroplasty, femoral
Impact of femoral analgesia on delirium nerve block provides analgesia comparable to epidural analgesia, but induces fewer side effects or complications [12]. It has been suggested that the analgesic effect of this technique is due to the cephalic spread of the local anesthetic inside the psoas compartment, reaching the lumbar plexus [13]. Nevertheless, in our opinion, it is necessary to use a multimodal approach to ensure the success of the analgesia. Baseline medication in the present study consisted of analgesics known to induce delirium in the elderly either to only a minimal degree or not at all. Previous investigations have shown that in postoperative pain treatment following knee or hip arthroplasty, fentanyl was almost equal to morphine on pain relief with a 10% lower occurrence rate of delirium [14]. In contrast, hydromorphone [15] and particularly meperidine [16] showed a substantial frequency of delirium in the postoperative time period. The 3-glucuronide metabolites of both morphine and hydromorphone can lead to neuroexcitation, whereas fentanyl undergoes hepatic biotransformation to inactive metabolites. Morphine also undergoes hepatic conjugation to form morphine 6glucuronide, an opioid agonist. Although some studies have examined the relative analgesic efficacy and adverse effects profile of morphine compared to morphine 6-glucuronide, none has evaluated their impact on postoperative delirium. In how far rescue medication of morphine given to patients treated with conventional analgesics contributed to the higher occurrence of delirium in the presented study remains speculative but this aspect cannot be excluded. Still, the fact that there is a remote chance that morphine and many other opioids may lead to a higher occurrence of delirium justifies a regional analgesic technique and as demonstrated in the present investigation preferably a peripheral one.
4.1. Limitations of this study Patients were classified as having developed delirium if there was documentation of altered mental status either in the medical record or in the nursing record. We did not use screening tools to identify cognitive disorders as confusion assessment method [17]. It is a recognised tool but it is a punctual measurement. Therefore we also compiled the alterations undergone during the night, when episodes of delirium are more frequent. Using screening tools allows us potentially to diagnose cognitive disturbance without agitation. Probably this kind of disturbances does not impact on surgery outputs. Other weakness of the study could be that we did not assess pain by Numeric Scale or Visual Analogic
63 Scale. We used an indirect method, as consumption of opioids. The retrospective nature of our study did not allow us to have this data. The average age of our patients was 81 years old, which makes VAS assessment difficult or impossible in many cases. Elderly patients with delirium might not effectively communicate VAS score. Pain evaluation might be inaccurate in elderly patients with pre-existing cognitive dysfunction or cultural barriers, and thus in turn might lead to inappropriate analgesic dosing or to confuse pain with delirium. Demonstrated risk factors of delirium are gender, previous dementia and general anaesthesia [4]. We did not exclude patients with previous dementia or with previous use of antipsychotic drugs, what could be a methodological flaw, but we only found one case of Alzheimer disease in Group 2 (NO femoral). Patients age, previous ambulatory and living status, previous dependence in basic and instrumental activities of daily living, medical comorbidities, and fracture type did not influence the appearance of delirium. There are many other factors that could impact in the development of cognitive disturbances but they have not been studied, such as time between fracture and surgery, duration of surgery, previously use of antipsychotic drugs and drug interactions. In conclusion, it appears that a combination of a local anaesthetic administered by means of a femoral catheter and intravenous paracetamol and metamizol could be superior to a conventional pain treatment consisting only of the two latter drugs. Patients treated conventionally required significantly more rescue morphine analgesia than did those receiving a multimodal (femoral catheter + IV paracetamol/metamizol) therapy. Additionally, opioids themselves carry a higher or lower risk of producing delirium depending on their metabolite profile. It remains to be seen if future studies on peripheral nerve analgesia can confirm the present results of reduction of postoperative delirium a postoperative complication frequently seen in the elderly patient population.
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