Abstract

Background

Epidural analgesia is widely used for efficient pain relief after major surgery. However, it may cause urinary retention, leading to delayed removal of bladder catheters with prolonged patient discomfort. Using a specific regimen in patient-controlled epidural analgesia (PCEA), we examined the optimal duration of urinary catheterization in patients undergoing major thoracic surgery.

Methods

Seventy-eight patients scheduled for elective thoracotomy were prospectively randomized into two groups: Group 1, removal of the transurethral catheter on the first postoperative day (n = 38); Group 2, removal of the catheter after discontinuation of PCEA (n = 40). The PCEA regimen was a mixture containing low-dose morphine, bupivacaine and neostigmine and was given for 3 days after surgery in all subjects. Micturition problems, pain scores assessed by the visual analog scale (VAS), and side effects were evaluated during and after PCEA treatment.

Results

The average duration of urinary drainage after surgery was 30.2 ± 5.1 hours and 78.5 ± 7.3 hours in Groups 1 and 2, respectively. After removal of the bladder catheter, no patient in either group required re-catheterization for urinary retention or encountered catheter-related infection. VAS scores were significantly lower in Group 1 at rest and at 24, 36 and 48 hours after cessation of PCEA. VAS scores were significantly higher in Group 2 patients, possibly due to catheter-induced pain related to prolonged catheterization.

Conclusion

Routine continuous bladder catheterization may not necessarily be required after thoracotomy in patients with ongoing continuous thoracic epidural analgesia.

Keywords

analgesia, epidural; analgesia, patient-controlled; thoracotomy; urinary catheterization; urinary retention;

1. Introduction

Pain following major thoracic surgery may increase the  risk  of  pulmonary  complications  without  ade-quate analgesia.¹ In recent years, continuous tho-racic epidural administration of opioids mixed with a  local  anesthetic  has  been  shown  to  provide effective analgesia and blockade of postoperative stress  response,  thus  potentially  reducing  pulmo-nary  complications  after  thoracotomy.²  However,  the side effects of opioids, such as respiratory de-pression, itching, nausea, vomiting and urinary re-tention are major concerns.^3,4 In particular, epidural local  anesthetics  and  opioids  may  inhibit  bladder function and lead to bladder catheterization as is common practice in patients undergoing major sur-gery,  and  may  iatrogenically  induce  urethral  dis-comfort, urinary tract infection, or urethral trauma and stricture.^5,6 There is still no consensus regard-ing the most appropriate catheterization strategy for  thoracic  epidural  analgesia.  Basse  et  al⁷  re-ported  that  bladder  catheterization  is  not  neces-sarily required for longer than 1 day after colectomy in cases with epidural analgesia. Kim et al⁸ showed that routine urinary catheters could be removed on postoperative  day  1  following  gastrectomy  in  pa-tients  who  were  receiving  thoracic  epidural  ropi-vacaine analgesia with supplemental sufentanil.

In our institute, a transurethral bladder cathe-ter is commonly inserted for urine excretion in pa-tients undergoing major surgery until termination of  thoracic  patient-controlled  epidural  analgesia  (PCEA). However, the issue of whether bladder cath-eterization  could  be  ceased  as  early  as  possible  after  lung  resection  with  postoperative  epidural  analgesia has not been solved. Thus, this prospec-tive randomized study was conducted to evaluate the best timing of urinary catheter removal during continuous PCEA therapy in patients having under-gone thoracotomy. We hypothesized that early re-moval of the bladder catheter after surgery might not cause acute urinary retention in patients treated with a mixed regimen of low-dose morphine, bupi-vacaine, and neostigmine for pain management.

Using  the  specific  PCEA  regimen,  the  present  study validated our hypothesis. Our results demon-strated that urinary catheter removal on the first day after thoracotomy was equally practical as wait-ing for 3 days when the epidural analgesia therapy was terminated, in terms of urinary  retention.

2. Methods

After obtaining approval from the Human Investi-gation  Committee  at  Kaohsiung  Veterans  General  Hospital and written informed consent from all pa-tients, 80 patients of ASA physical status I−III under-going thoracotomy were enrolled in this prospective, randomized study. Patients with known urological, spinal, cardiopulmonary, neurological diseases, co-agulopathy  and/or  any  medication  that  might  in-terfere  with  the  sympathetic  nervous  system  or  micturition were excluded from this study.

The sample size was predetermined using a power analysis based on the previous observation that the incidence  of  urinary  retention  would  range  from  0% to 80% in patients with spinal or epidural opio-ids. To achieve a power of 80% (1 − β) at the 5% sig-nificance level (α) to detect a reduction in urinary retention from 50% to 20%, which was considered to be of clinical importance, enrolment of 38 patients per group would suffice. Additionally, our previous study⁹ indicated that a sample size of 36 patients per group would yield an 80% chance (at α = 0.05)  of detecting a 30% reduction in pain intensity during activity on postoperative day 1.

On the day before surgery, patients were taught to use a visual analog scale (VAS, 0−10; 0 = no  pain, 10 = worst pain) and the PCEA device (Abbott Lab-oratories,  Abbott  Park,  IL,  USA).  Anesthesia  and  surgery  were  carried  out  in  similar  manner  in  all  subjects.  Before  inducing  anesthesia,  an  epidural  catheter  was  inserted  through  the  intervertebral  space  between  T5  and  T8  under  local  anesthesia  using a loss-of-resistance technique. Correct posi-tioning of the catheter was confirmed by injecting 3  mL  of  2%  lidocaine  with  1:200,000  epinephrine.  General  anesthesia  was  induced  by  intravenous  fentanyl (3 μg/kg), thiopental (5 mg/kg), lidocaine (1.5 mg/kg) and succinylcholine (1.5 mg/kg). After inducing anesthesia, a single dose of prophylactic antibiotic was given intravenously in all patients and a 14-F Foley catheter was inserted by the surgeon. Anesthesia was maintained with 1.5−2.5% isoflurane in oxygen/air mixture and atracurium was used for continuous muscle relaxation. Ventilation was me-chanically controlled to maintain the end-tidal CO₂ at around 35−40 mmHg. Hemodynamic parameters such as heart rate and arterial blood pressure were kept within 20% of baseline values by adjusting the concentration of end-tidal isoflurane.

For intraoperative preemptive analgesia, 0.25% bupivacaine was started via the epidural catheter at  an  infusion  rate  of  5  mL/hour  and  maintained  throughout surgery. At the end of surgery, thoracic PCEA  was  initiated  using  a  balloon  pain  manage-ment provider (Abbott Laboratories) to deliver an-algesic solution containing morphine (0.04 mg/mL), 0.08%  bupivacaine  (0.8  mg/mL)  and  neostigmine  (7 μg/mL).  The  PCEA,  which  was  designed  to  last  for 3 days, was set to offer a continuous infusion of  2.5  mL/hour  and  a  2.5-mL  bolus  dose  with  a  5-minute lockout period.

Postoperatively, the eligible patients were ran-domly  assigned  into  two  groups  according  to  a  table  of  random  numbers  generated  by  a  compu-ter: an experimental group (Group 1), in which the urinary catheter was removed on the first postop-erative day, and a control group (Group 2), in which the urinary catheter was removed after discontin-uation of PCEA (the third postoperative day). Pain intensity  during  cough  or  deep  breathing  (VAS-C)  and at rest (VAS-R) was assessed using the VAS sys-tem at 12-hour intervals for 6 postoperative days (POD  1−6).  The  PCEA  infusion  rate  and  bolus  vol-ume were adjusted according to the analgesic ef-fect or occurrence of side effects. If the pain relief was insufficient, the infusion rate and bolus volume were increased by 0.5 mL. If the patient experienced satisfactory pain relief, the settings were decreased daily by 0.5 mL. The infusion rate and bolus volume were restored to the previous level if breakthrough pain occurred after the adjustment. If the patient could not endure the pain (VAS-R > 4), the epidural insertion  site  was  examined  to  see  whether  the  catheter had migrated, and 7 mL of lidocaine (1%) was administered epidurally to see whether the an-algesic effect could cover the surgical area. Daily analgesic consumption and side effects such as nau-sea,  emesis,  pruritus  or  urethral  discomfort  were  recorded.  Severe  nausea  or  vomiting  was  treated  with dexamethasone (5 mg), and severe pruritus was treated with intravenous chlorpheniramine maleate (10 mg) every 8 hours if required. All patients were questioned about their ability to urinate. If acute urinary retention occurred 6 hours after removing the urinary catheter, the bladder was drained with in-and-out catheterization.

2.1. Statistical analysis

All  values  were  presented  as  mean  ± standard  de-viation. Statistical analyses were performed using SPSS version 11.0 (SPSS Inc., Chicago, IL, USA). Pa-tient  characteristics  were  analyzed  using  χ2  tests  (or  Fisher’s  exact  test)  and  unpaired  t  tests.  Dif-ferences  between  and  within  groups  were  evalu-ated using the Mann−Whitney U test with Bonferroni correction. A p value < 0.05 was considered to be statistically significant.

3. Results

We included 80 patients in this study, of whom two patients  in  Group  1  were  excluded  due  to  inad-equate  pain  relief  by  postoperative  PCEA;  these  two  patients  used  intravenous  analgesia  instead.  Patient characteristics and perioperative data are summarized in Table 1. The two groups in this study were similar with respect to age, weight, height, sex,  operation  time,  fluid  amount,  urine  output  and blood loss.

The  average  duration  of  bladder  drainage  was  30.2 ±  5.1  hours  and  78.5  ±  7.3  hours  in  Groups  1  and  2,  respectively.  Comparison  of  pain  intensity  during cough or deep breathing (VAS-C) and at rest (VAS-R)  between  the  two  groups  are  shown  in  Figures 1 and 2. All subjects represented the VAS-R scores  as  below  4,  indicating  that  the  postopera-tive pain management was comparable. However, VAS-R  scores  were  significantly  lower  in  Group  1  vs. Group 2 at 24 hours (0.47 ± 0.10 vs. 0.85 ± 0.18, p <   0.05),   36   hours   (0.39   ± 0.08 vs.   0.63   ± 0.11, p < 0.05), and 48 hours (0.21 ± 0.50 vs. 0.57 ± 0.10, p < 0.05) after cessation of PCEA (Figure 2). The VAS scores for catheter-induced urethral pain were sig-nificantly  higher  at  48−84  hours  after  surgery  in  Group 2 (Figure 3, p < 0.05). There was no difference in  the  incidence  of  side  effects  such  as  nausea,  vomiting or pruritus between groups (Table 2). No patients in either group needed re-catheterization for urinary retention after removal of the bladder catheter or experienced catheter-related infection. Both groups showed similar daily analgesic use after surgery (Figure 4).

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Figure 1 Incision wound visual analog scale scores during cough or deep breathing (VAS-C) were assessed at 12-hour intervals for 6 days after surgery. Patient-controlled epi-dural analgesia (PCEA) was discontinued on postoperative day 3.

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Figure 2 Incision wound visual analog scale scores at rest (VAS-R) were assessed at 12-hour intervals for 6 days after surgery. Patient-controlled epidural analgesia (PCEA) was discontinued on postoperative day 3. The VAS-R scores for incision pain at 24, 36 and 48 hours after termination of PCEA were significantly lower in Group 1 patients in whom the urinary catheter was removed on postoperative day 1 than in Group 2 patients in whom the catheter was removed after discontinuation of PCEA. *p < 0.05.

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Figure 3 Visual analog scale (VAS) scores of urethral pain were assessed at 12-hour intervals for 4 days after surgery. Patient-controlled epidural analgesia (PCEA) was discontinued on postoperative day 3. The urethral VAS pain scores were significantly higher at 48, 60, 72 and 84 hours after surgery in Group 2 patients in whom the catheter was removed after discontinuation of PCEA. *p < 0.05.

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Figure 4 Accumulative consumption of patient-controlled epidural analgesia (PCEA) for 72 hours after surgery. There were no statistically significant differences between groups

4. Discussion

Removal of the bladder catheter 1 day after thora-cotomy  was  preferable,  even  under  a  regimen  of continuous epidural analgesia with low-dose mor-phine,  bupivacaine  and  neostigmine,  because  no  episodes  of  acute  urinary  retention  or  catheter-related  infection  occurred.  Short-term  bladder catheterization  was  associated  with  less  urethral  discomfort and less pain, which suggests that dis-continuation  of  urinary  drainage  by  catheter  on  postoperative day 1 was a meaningful decision.

Postoperative urinary retention remains a signifi-cant clinical problem, with a reported incidence of between 10% and 60% after major surgery.^10,11 The pathogenesis of micturition dysfunction after sur-gery is multifactorial and is related to the category of surgery, type of anesthesia, drugs used, and stress-induced  activation  of  inhibitory  sympathetic  re-flexes.⁷ To prevent detrimental effects on bladder function after major surgery, perioperative urethral catheterization should be performed, particularly in patients with ongoing epidural analgesia.

Previous studies have stressed that intrathecal or  epidural  anesthesia  increased  the  incidence  of  urinary  retention,  mainly  when  opiates  were  used.¹²⁻¹⁴  Rawal  et  al¹⁵  showed  long-lasting  im-pairment of detrusor contractility after lumbar ad-ministration  of  2,  4  or  10  mg  epidural  morphine.  The  mechanism  for  voiding  dysfunction  seems  to  be related to inhibition of bladder afferents at the dorsal  horn  by  spinal  opioids.  In  addition,  acti-vation  of  μ-receptors  located  in  the  sacral  para-sympathetic  nervous  system  attenuates  bladder  sensation and may delay the initiation of the mic-turition  reflex,  which  is  normally  induced  as  the  volume exceeds the micturition threshold, and leads to  detrusor  muscle  relaxation  and  an  increase  in  maximal bladder capacity.¹⁶

Despite  highly  effective  control  of  postopera-tive pain, the potential for urinary retention with epidural  opioids  makes  clinical  decisions  diffi-cult.^1,17 Some studies have been conducted to eval-uate the optimal duration of bladder drainage by a catheter during continuous epidural analgesia after major  abdominal  surgery.  Basse  et  al⁷  reported  a  low incidence (9%) of urinary retention after cath-eter  removal  on  the  first  postoperative  morning  (approximately 16−20 hours after colonic resection), indicating  that  the  duration  of  routine  bladder  catheterization might not exceed beyond 24 hours after surgery, even in the presence of low-dose local anesthetic opioid-based epidural analgesia. Similar results  were  found  in  the  study  by  Kim  et  al,⁸ where  only  3.3%  of  patients  showed  urinary  re-tention  on  the  second  postoperative  day  during  analgesia with epidural ropivacaine and morphine. Nevertheless,  the  most  appropriate  duration  of  urinary  catheterization  after  major  thoracic  sur-gery in patients receiving continuous epidural an-algesia remains uncertain.

Using a combination of morphine, bupivacaine and neostigmine for PCEA for relief of postoperative pain after thoracotomy, we found no occurrence of void-ing difficulties needing bladder re-catheterization (intermittent or persistent indwelling) after removal of the Foley catheter on the first postoperative day. We suggest that this favorable result can be attri-buted  to  improved  epidural  segmental  analgesia,  which was restricted to T5−6 dermatomes, corre-sponding to the incision area with little territorial interference  in  detrusor  contractility  (S2−S4)  and  micturition reflex. Reduction of the stress-induced suppressive sympathetic nerve reflexes after satis-factory pain relief may also be involved. Thus, based on our results, we believe that the urinary catheter, even during PCEA therapy, can be removed earlier than is commonly done. This concept is important because urinary tract infection as a result of pro-longed  bladder  catheterization  is  associated  with  an almost threefold increase in mortality in hospi-talized patients.¹⁸ Benoist et al¹⁹ reported that re-moving the urinary catheter on the first day after surgery significantly reduced the incidence of post-operative urinary tract infection from 42% to 20% when the catheter was removed after 5 days.

Of note, we used neostigmine, a cholinesterase inhibitor,  as  an  adjuvant  for  epidural  analgesia.  Neostigmine, after preclinical toxicity screening,²⁰ was  first  introduced  to  clinical  trials  in  1995  for  intrathecal injection.²¹ Intrathecal neostigmine, be-cause  of  its  ability  to  prevent  degradation  of  the  central neurotransmitter acetylcholine within the spinal cord, is recognized to produce analgesia in patients  with  chronic  pain²²  and  acute  pain  after  surgery²³  due  to  increased  acetylcholine  in  the  medulla  spinalis,  which  binds  all  muscarinic  and  nicotinic receptors and stimulates nitric oxide syn-thesis.²⁴ However, the high incidence of nausea and vomiting limits its clinical usefulness by this route of  administration.  More  recently,  epidural  admin-istration of neostigmine has been demonstrated to improve  postoperative  analgesia  in  most  clinical  studies without increasing the incidence of adverse events.²⁵⁻²⁹ Lauretti et al³⁰ found that epidural ne-ostigmine (1, 2 or 4 μg/kg) combined with low-dose lidocaine  produced  a  dose-independent  analgesic  effect after orthopedic surgery. Our previous study also demonstrated that supplemental neostigmine in  PCEA  regimens  reduces  the  postoperative  dose  of epidural bupivacaine and fentanyl by 13.5%.9 It is  conceivable  that  neostigmine  potentiates  epi-dural anesthetics via the spinal mechanism of ac-tion;  it  may  be  absorbed  to  systemic  blood  flow  through  the  epidural  venous  plexus,  and  possibly  blocks  nociception  by  stimulating  the  cholinergic  receptors  in  the  brain.³¹  Systemic  administration  of cholinergic agonists also cause increased intra-vesical pressure in the bladder,³² which may be at least partially responsible for our favorable results in terms of micturition.

We  acknowledge  some  potential  limitations  in  the present study. First, the duration of catheteri-zation between the two groups was not identical. Second, the results presented in this study reflect a  unique  regimen,  which  may  not  be  appropriate  for  other  types  of  surgery,  patients,  or  analgesic  treatment. Finally, neither the subjects nor the as-sessors were blinded to the postoperative micturi-tion assessment. Therefore, randomized controlled clinical  studies  or  large  prospective  studies  with  well-defined  treatment  regimens  may  be  needed  in the future.

In conclusion, our findings show that continuing urinary catheterization after thoracotomy was not necessary, even during active PCEA. We suggest that it  could  be  safe  and  appropriate  to  remove  the  Foley catheter on the first postoperative day after thoracotomy.