Abdominal hysterectomy is a procedure that causes pathophysiological effects similar to other lower abdominal laparotomies. Among the immediate complaints, an increased level of acute pain and postoperative nausea and vomiting (PONV) are apparent because of psychological and gender-specific causes [1–3]. From this premise, abdominal hysterectomy and its many perioperative aspects have naturally been the focus of much research, but the quality of combined perioperative care remains unsatisfactory in terms of acceptable reductions in pain, PONV and restoration of normal autonomy. An overall assessment of a multimodal regime is warranted to address the unmet needs that still cause problems for patients and caregivers  (www.postoppain.org.). We have undertaken an observational study of consecutive patients scheduled for abdominal hysterectomy with an evidence-based anaesthetic/analgesic regime to evaluate the current status of postoperative complaints, their possible interactions, the efficacy of prophylactic treatments and the applicability of a structured multimodal regime in a busy anaesthesia department.
Aim of the study
The aim of the current observational study was to
- describe the content, applicability and efficacy of our current multimodal anaesthetic regime, and how it relates to pain, PONV and length of stay in the postanaesthesia care unit (PACU),
- describe risk factors that impede normal postoperative recovery and how they may correlate to each other,
- describe the clinical impact of postoperative pulmonary dysfunction in the PACU after abdominal hysterectomy.
All consecutive patients admitted for elective abdominal hysterectomy at Hvidovre University Hospital between 1 January 2005 and 30 September 2005, were included in the study. Reasons for hysterectomy were fibroma uteri (40%), carcinoma of the cervix or uterus (32%), vaginal bleeding abnormalities (18%) and ovarian cysts/hydrosalpinx (10%). All patients underwent the procedure using the Pfannenstiel incision.
We have tried to tailor the preventive treatment measures according to the available evidence, well knowing that there are limits to our current knowledge. To some extent we have had to extrapolate results from studies in populations of mixed sex to the female population of the current cohort (www.postoppain.org.).
The aim of the multimodal anaesthetic regime is to optimize postoperative pain control and PONV prevention on the basis of current evidence and, in the case of epidural analgesia, less opioid requirements and better pulmonary function, although the evidence for this method is arguably limited. The use of both a NSAID and paracetamol for premedication is likewise debatable but has been included for optimization purposes. Remifentanil is employed for absolute intraoperative pain reduction, and the use of two opioids in the PACU is to combine a fast-acting and a long-acting drug. Three antiemetics have been employed for preventive purposes, and we have opted to reuse ondansetron and droperidol for PONV treatment, from the standpoint that their lack of efficacy may be caused by insufficient dosages. For a further description of the intraoperative anaesthetic plan and the postoperative regime, see Table 1.
Once intubated, the patient received volume-controlled ventilation with a tidal volume of 7–10 ml kg−1 and a frequency of 10–12 min−1, with a 1: 2 mix of oxygen and air in a closed system. PEEP was given at the discretion of the anaesthesiologist. Once in the PACU, analgesics (initially i.v. sufentanil 10 μg or epidural bupivacaine 0.25% 5 ml, then i.v. morphine 10 mg) were administered on an ‘on request’ basis for visual analogue scale (VAS) above 3 on a 0–10-point scale, and antiemetics (ondansetron, droperidol) likewise. Patients were specifically questioned for PONV complaints at 15-min intervals. The protocol for administration of additional analgesics was to abate initial pain complaints with sufentanil combined with morphine, then reevaluate and readminister at 15-min intervals, if insufficient; the attending nurse was also able to administer these drugs independently according to patient needs. The lesser dose of morphine on secondary pain complaints was generally used if the patient seemed fragile and/or had less intense pain complaints. Epidural analgesia was supplied as a top-up dose on the initial pain request, and once more if needed. Patients requiring large amounts of analgesics (generally more than 30 mg morphine i.v.) were discharged with the epidural catheter intact, at the discretion of the anaesthesiologist. Oral fluids were given at the patient's request, and binasal oxygen supply was administered if the oxygen saturation (SpO2) was less than 92%. Patients were monitored by three-lead ECG, pulse oximetry and clinical observations on admittance and, at minimum, every 15 min. All vital signs were monitored continuously until discharge. The patient was discharge ready when she was able to achieve a modified Aldrete  score of 13 out of 14 (Table 2) .
For purposes of a dichotomous analysis, patient recovery outcomes are divided into two groups: uncomplicated recovery and complicated recovery. A complicated recovery profile is intended as a meaningful parameter to align both patient-relevant and logistically relevant endpoints into one, and will be defined as severe pain and/or PONV, and/or more than five interventions in the PACU, and/or actual length of stay at the PACU more than 120 min. These cut-off points for PACU observations have been employed by other investigators . Severe PONV, severe pain and severe pain and/or PONV are defined as 1 h or more of either or both complaints present during the PACU stay. Interventions are defined as any drug or new intravenous fluid administration given by the staff during the PACU stay, in addition to standard observation, oxygen administration and continuance of ongoing fluid therapy.
In order to evaluate the influence of nonpulmonary complaints, both ‘time of actual discharge’ and ‘time of discharge readiness without SpO2 requirement’ are presented. Contrary to actual discharge, discharge readiness without SpO2 requirement will be defined by a modified Aldrete score on two consecutive observations of at least 11 out of 12 points with no obvious need for further medical or fluid treatment or observation, excluding the SpO2 subscore otherwise used in Table 2.
All outcome variables were defined prior to data collection. Some were in accordance with data sets from previous studies, whereas others were based on experiences from our anaesthetic unit. Results are presented in a descriptive fashion and as comparisons between groups. For comparisons, the relative risk (RR) of each characteristic between the groups is also presented. The unpaired Student's t-test for means difference is used for continuous data, whereas 95% confidence intervals in a fixed effects model are used for dichotomous data with the RevMan 4.2 software. A two-sided P < 0.05 is considered significant. Data are presented using all-patients-treated analysis, which includes patients that follow the preplanned treatment fully, and those that for any reason are treatment noncompliant (Table 3).
Out of 145 patients, complete data sets were available for n = 142. Nine percent had a minor omission in the preplanned analgesic/antiemetic treatment (sufentanil, dexamethasone, droperidol and ondansetron), and 13% did not receive the preplanned epidural block, because of refusal, technical difficulties, coagulation disorders or unjustified omissions. Only 3% of all patients had more than one omission. Patient characteristics and intraoperative treatments for the entire cohort are presented in Table 4.
In the PACU, 57% were pain-free, and 64% did not require additional opioids. Twenty-five percent experienced severe pain that required both sufentanil and morphine. Mean sufentanil demand was 8 μg (range 0–70 μg), and mean morphine demand was 3 mg (range 0–50 mg). Opioid demand was considerably greater in the cohort not receiving an epidural block. Sixteen percent required more than five interventions in PACU in which mean length of stay was 119 min (range 30–270 min) and 44% stayed longer than 2 h. Sixteen percent (3/19) of those initially refusing an epidural agreed to an epidural in the PACU. Ten percent of all patients were discharged from the PACU with a continuous epidural infusion to the step-down unit. Mean duration of oxygen demand in the PACU was 65 min (range 0–270 min), with 47% requiring oxygen for 1 h or more. For the entire cohort, 48% had an uncomplicated postoperative recovery, and for the cohort with epidural analgesia, this level of efficacy was 54%. Eight percent experienced PONV, half of which was of short duration.
Quality of the intraoperative regime and its impact
Nine percent had deviations from the standard procedure that were not justified in the condition or demands of the patient; most such deviations were omissions in dexamethasone or droperidol. The impact of these omissions was, however, limited, because the prevalence of deviations in complicated and uncomplicated recoveries in the cohort receiving epidurals was similar (data not shown). Omission of intraoperative epidural analgesia by refusal or technical difficulties was, however, a major determinant for complicated recovery (17 of 19 patients not given epidurals had a complicated recovery).
Characteristics of a complicated postoperative recovery
Table 4 displays the characteristics of the entire cohort (n = 142). Complicated cases distinguish themselves by having a longer duration of surgery, fewer epidurals, increased oxygen demand, more pain, more PONV and more analgesic demands. More patients required continuous epidural infusion to manage pain after PACU. When isolating patients with epidurals, these qualitative differences remain unchanged.
Postoperative pain was observed in 43% of the patients, with about half of the patients experiencing severe pain (Table 4). Patients given epidurals were slightly older than patients not given epidurals (Table 5); otherwise preoperative and intraoperative characteristics were similar. Postoperative complaints differed significantly, with patients not receiving epidurals having greater demand for supplemental oxygen, pain and PONV treatments. Patients not receiving epidurals both experienced pain more frequently and more severely, with greater analgesic demands. This was likewise reflected in the mean number of interventions necessary and length of stay. In patients given epidurals, 10/123 had postoperative motor block lasting for about 1 h.
Patient characteristics and perioperative factors vs. postoperative pulmonary function
Extended oxygen demands (≥1 h) occurred in 47% of the entire cohort (Table 4). Oxygen demand did not relate to duration of surgery, BMI or ASA classification, but correlated positively to number of interventions, length of stay and treatment of pain.
Considering the multitude of anaesthetists and nurses performing the anaesthetic procedures and the many strict treatment guidelines in our cohort, we have shown that it is possible to maintain a high quality of treatment adherence (>90%) for a multimodal clinical pathway in the entire perioperative setting. High treatment compliance requires conviction and attention to the value of the regime by all of those involved, but standardization helps reduce errors of neglect.
Length of postanaesthesia care unit stay
Our cohort is representative of most studies on abdominal hysterectomy in terms of patient demographics and duration of surgery . Length of PACU stay following abdominal hysterectomy has not been investigated in depth and may depend on logistical considerations and step-down facilities. In a previous study on 40 hysterectomies, mean length of stay was 2.5 h . Our primary concern, however, was to optimize patient abilities to transit to normal autonomic function including mobilization, food and fluid intake, and restore normal cognitive function as fast as possible . We were able to reduce average PACU stay to 2 h with the requirement of SpO2 greater than 92%, and average discharge readiness without this requirement (comparable to a discharge with binasal oxygen supply) to less than 80 min. The discrepancy between these values reflects a minor oxygen demand without the presence of other complaints, and therefore underlines the need for further study into the clinical relevance of this transient pulmonary disturbance.
Postoperative nausea and vomiting
Randomized studies have shown that postoperative nausea and vomiting in the first 24 h may be consistently reduced to less than 20% with combinational therapies of serotonergic inhibitors, low-dose droperidol, dexamethasone and/or intravenous anaesthesia [9–12]. Our regime consists of total intravenous anaesthesia with propofol–remifentanil, and three intraoperatively administered prophylactic antiemetics, dexamethasone 8 mg, ondansetron 4 mg and droperidol 0.625 mg i.v. Only 8% of our patients experienced any PONV in the PACU, of which half was easily managed (Table 4). Only 7% of the complicated cases were due to PONV.
Weak analgesics (NSAIDs, cox-2 inhibitors, paracetamol and tramadol) have been shown to be effective in reducing pain and opioid requirements. When given intraoperatively or postoperatively, they reduce morphine requirements on the first postoperative day by 17–47% (www.postoppain.org.) [13–19]. Evidence of an increased effect when combining weak analgesics is, however, based on few randomized studies [20,21]. Our multimodal regimen consists of preoperative oral slow-release paracetamol 2 g and celecoxib 200 mg, both of which were continued after discharge from the PACU. Both drugs are long-lasting, securing a clinically relevant plasma concentration in the PACU, and a cox-2 inhibitor was used to reduce the possible risk of perioperative bleeding disorders .
Remifentanil is employed for absolute intraoperative pain reduction, and the use of two opioids (sufentanil and morphine) in the PACU is to combine a fast-acting and a long-acting drug. Opioids are clearly the most effective postoperative analgesics but also problematic in terms of their many side effects. The group not receiving epidurals was uncontrolled and may not be representative for the entire cohort; this clearly limits the assessment of the value of epidurals in abdominal hysterectomy. Our results should be viewed with caution and are, at best, indicative of potential PACU complaints with or without an epidural. Apart from an increased opioid demand, the patients without epidurals had more PONV (21 vs. 6%), longer oxygen demand (111 vs. 57 min), more interventions (7.5 vs. 2.1) and longer time to discharge readiness (114 vs. 71 min) (Table 5). It seems likely that the opioid therapy contribute to these findings. An opioid-free regimen is not applicable to the actual kind of surgery, suggesting that other adjuvant analgesics or continuous wound infusion of local anaesthetics may be relevant in future multimodal treatment pathways.
Some studies on major colonic surgery have shown that intraoperative remifentanil (at 0.3–0.4 μg kg−1 min−1) may cause postoperative hyperalgesia [23,24]. The impact on pain and opioid requirements in the PACU does, however, seem limited, and since both a study on hysterectomy patients  and other investigators cannot replicate these results, the evidence is at best equivocal that remifentanil has a clinically relevant negative impact on postoperative pain in the PACU.
Clinical studies confirm that epidural bolus local anaesthetics and morphine as bolus injections at closure and as postoperative continuous infusions reduce pain, opioid demands and stress hormones for up to 24 h, and possibly reduce PONV [26–33]. Patients receiving epidurals had less severe pain in the PACU, less opioid demands and shorter duration of stay (actual discharge: 113 vs. 161 min, P > 0.05). Although PONV was seen less frequently in the epidural cohort (any PONV: 21 vs. 6%, P > 0.05), our results clearly show that residual postoperative pain is the primary dividing factor between the epidural and nonepidural groups, the treatment of which influences both oxygen demands and interventions in the PACU. The invasiveness and the – albeit rare – neurologic risks of the technique do, however, question the use of neuraxial anaesthesia in abdominal hysterectomy (www.postoppain.org.). Despite the epidural regime, 19% experienced severe pain in the PACU. Responsible for this problem may be the volume and concentration of bupivacaine being inadequate. Nevertheless, a higher concentration of bupivacaine would increase the likelihood of motor block which may impede mobilization. Our patients received 69 top-up doses of bupivacaine 0.25% 5 ml in the PACU; 11% (14/123) required more than one top-up dose, and most of these (11/14) were associated with extensive opioid demands, suggesting lack of analgesic effect.
Pulmonary dysfunction after general anaesthesia and abdominal procedures is well known [34–36]. Forty-seven percent of the patients had an increased oxygen demand for 1 h or more in the PACU to sustain SpO2 more than 92% (Table 4; criteria defined by the Danish Society of Anaesthesia and Intensive Care). The patients receiving epidural blockade had less mean oxygen demand, less ‘time to discharge readiness without SpO2 requirement’ and less ‘length of stay’ compared to nonepidural patients (Table 5). Considering the strong relationship between oxygen demand and opioid analgesia, it seems evident that future treatments should target nonopioid, multimodal analgesia for faster recovery of normal respiratory function.
We conclude that a well defined multimodal anaesthetic regimen can be implemented in a large anaesthesia department with unjustified deviations in only 9% of the patients. Major determinants of PACU length of stay were pain, opioid demands and extended oxygen requirements, whereas PONV had limited impact. Transient pulmonary dysfunction, seen clinically as reduced SpO2 values, occurred in half the patients.
Future research strategy
The results suggest that antiemetic therapy was sufficient, but improved analgesia is required. Supplemental pain treatment may include adjuvants such as gabapentin or pregabalin [37–39], low-dose ketamine , clonidine [29,41], lidocaine [42,43], continuous incisional local anaesthetics  and psychological interventions [2,45,46]. Further insight into early postoperative pulmonary dysfunction and the need for an SpO2 more than 92% [23,34,37,47] is also warranted.
There are no financial interests or sponsorship involved in the undertaking of this study.
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