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From the *Department of Anesthesia and Critical Care, Université Paris-Descartes, Faculté de Médecine, Assistance Publique–Hôpitaux de Paris, Hôpital Cochin, Paris Cedex, France; Department of Anesthesiology and Pain Management, University of Texas, Southwestern Medical Center at Dallas, Dallas, Texas; and Department of Anesthesiology, CHP Saint-Grégoire, Saint-Grégoire, France.
Address correspondence and reprint requests to Claude Lentschener, MD, Department of Anesthesia and Critical Care, Hôpital Cochin, 27 rue du Faubourg Saint Jacques, 75679 Paris Cedex 14, France. Address e-mail to claude.lentschener{at}cch.aphp.fr.
Abstract
BACKGROUND: Sedation can occur during intravenous titration of morphine for acute pain control in the postanesthesia care unit (PACU). We designed this case-control study to evaluate the relationship between opioid-induced sedation in the PACU and adequacy of early postoperative analgesia.
METHODS: Intravenous morphine was titrated in 2 mg (body weight 
60 kg) or 3 mg (body weight >60 kg) boluses every 5 min to treat moderate-to-severe pain in the PACU. Pain was assessed using a 11-point verbal rating scale (VRS) with scores 
3 representing moderate-to-severe pain. The 6-point Ramsay score was used to assess the level of sedation with scores >3 representing clinically significant sedation. Twenty-six patients, with a Ramsay sedation score >3 and a pain VRS 3 at discharge from the PACU, were evaluated 24 h after surgery to assess (a) the recall of early postoperative pain in the PACU, (b) quality of sleep on the first night after surgery, (c) pain on the 24th postoperative hour, and (d) satisfaction with pain management at 24 h after surgery. Two patients discharged from the PACU with VRS pain scores <3 were matched to each of the patients with pain scores 3 and Ramsay score >3, as part of a 52 patient control group.
RESULTS: Patients with Ramsay scores >3 and pain scores 3 more frequently reported moderate-to-severe pain in the PACU (severe/moderate/no pain: 18%/25%/57% vs 58%/16%/26%, P = 0006, for the control and the sedated group, respectively), poorer quality of sleep the night after surgery (well/moderate/bad: 48%/42%/10% vs 23%/23%/54%, P = 0.001, for the control and the sedated group, respectively), and higher pain scores at the 24th hour after surgery (severe/moderate/no pain: 6%/44%/50% vs 50%/42%/8%, P < 0.0001, for the control and the sedated group, respectively). In addition, their overall satisfaction with pain control during the first 24 postoperative hours was lower (satisfied/moderately satisfied/not satisfied: 96%/2%/2% vs 50%/30%/20%, P < 0.0001, for the control and the sedated group, respectively).
CONCLUSION: Clinically significant opioid-induced sedation in the PACU does not insure adequate self-reported pain relief.
Self-assessment of pain using numerical analog scales is routinely used in postanesthesia care units (PACUs) to evaluate the sensory component of the pain experience, and to control the efficacy of intravenous (IV) morphine titration (1). Sedation often occurs during IV morphine titration in the PACU (2,3). Sedation is a criterion for withholding additional IV morphine administration (3,4). Twenty-five percent of deeply sedated PACU patients were reported to have high pain scores when verbally stimulated, even though IV morphine had been administered (2). Amnesia of painful perioperative circumstances has been reported after different types of non-opioid pharmacologic sedation, and has been assumed to have accounted for patient satisfaction after incomplete pain care (5). Whether sedation occurring during IV morphine administration in the PACU is synonymous with efficient early postoperative pain control or amnesia of postoperative pain has never been investigated (2,3).
The aim of the present case-control study was to test the hypothesis that deep sedation with a high pain score in the PACU is not synonymous with efficient pain control. To test this hypothesis, 24 h after surgery, we prospectively evaluated (a) whether patients who were discharged from the PACU in a highly sedated state with high pain scores after IV morphine titration, remembered a painful experience associated with the early postoperative period, and (b) if they still experienced more postoperative discomfort 24 h after surgery than morphine-titrated patients undergoing the same operation and discharged from the PACU with no pain.
METHODS
This study was approved by the Hospital Ethical Committee (CCP Paris-Cochin) and was conducted over 3 months in the local university department of anesthesia. Since the data were recorded without any specific intervention and using an existing protocol in the PACU, the Ethics Committee agreed to waive informed consent.
The study was conducted on consecutive patients admitted to the PACU after elective surgical procedures who received an IV morphine titration. The criteria for exclusion included patients already receiving nonsteroidal antiinflammatory drugs or opioids for significant preoperative pain; with minor postoperative pain defined by a pain verbal rating scale (VRS) score <3 that did not require morphine titration in the PACU; with delirium, dementia, already sedated (Ramsay score >3) when arriving in the PACU; who were non-French speaking or who did not understand the VRS score; and interruption of morphine titration because of the occurrence of severe adverse effects, or concomitant administration of other analgesics including regional anesthesia. During the preoperative visit, patients were familiarized with the 11-point VRS as a method of assessing postoperative pain (1–4,6–8). Patients received, as oral premedication, hydroxyzine 1.5 mg/kg, 90 min before induction of general anesthesia (GA). GA was conducted using propofol, sufentanil, isoflurane, and atracrium. One hour before the expected end of surgery at the discretion of the attending anesthesiologist, IV ketamine 0.1–0.15 mg/kg was administered over 60 min in patients undergoing major abdominal surgery, and all patients received IV acetaminophen 1 g, and IV ketoprofen 50 mg or nefopam 20 mg when ketoprofen was contraindicated (9,10). An additional dose of this analgesic combination was systematically administered four times a day for the first 48 postoperative hours. After surgery, all patients were admitted to the PACU and received oxygen 4 L/min via a facemask. Time of arrival in the PACU, as indicated by the nurse in charge of the patient in the clinical report, is considered as time 0 in the PACU for further assessment. Clinical monitoring included measurement of vital signs, and sedative level using the Ramsay score (11). The 6-point Ramsay score assesses the sedation level: 1 = anxious and agitated patient; 2 = cooperative patient; 3 = sleeping patient, brisk response to loud voice; 4 = sleeping patient, sluggish response to loud voice; 5 = no response to loud voice; 6 = no response to pain (11). Clinically significant sedation was defined by a Ramsay score >3. The depth of sedation was assessed every 5 min together with pain assessment during IV morphine titration. After tracheal extubation and when awake, patients were questioned about the intensity of their pain at 5-min intervals. PACU nursing staff has been trained to assess pain using the VRS scoring system and to perform IV morphine titration using a previously validated protocol (3,4,12). The pain VRS ranges from 0 = no pain to 10 = the worst imaginable pain (4). Pain was considered to be moderate-to-severe if the pain VRS score was 3 (3,4). Adequate pain relief was defined as a pain VRS of <3 (3,4). If the patient was asleep, he or she was awakened and asked to assess pain intensity. When the pain was too severe to obtain a pain VRS, it was arbitrarily scored 10, and the pain was assessed later. The pain was assessed every 5 min until pain relief during IV morphine titration. Morphine titration was initiated when the VRS pain score was 3. The IV morphine was titrated in 3 mg increments for patients weighing >60 kg and 2 mg for patients weighing 60 kg (3,4,12). There was no upper limit to the total administered dose of morphine (4,12). Morphine titration was discontinued when pain VRS was <3 and in the event of side effects such as nausea and/or vomiting, cutaneous rash, severe pruritus, the occurrence of deep sedation (Ramsay score >3), a respiratory rate <10/min, or Spo2 <94% while receiving supplemental oxygen. Patient-controlled analgesia (PCA) or subcutaneous morphine administration was implemented after IV titration at the discretion of the attending anesthesiologist when the patients were discharged to the ward.
Twenty-four hours after surgery, eligible patients with a Ramsay score >3 and a VRS 3 after IV morphine titration in the PACU were interviewed in the ward by a nurse blinded to early postoperative pain assessment and asked the following questions: (a) How are you this morning? (good, bad); (b) How is your pain this morning? (severe, moderate, no pain); (c) Yesterday, how was your pain when you arrived in your room? (severe, moderate, no pain); (d) How did you sleep last night? (well, moderately, badly); (e) Are you satisfied with the pain care provided during the first 24 postoperative hours? (yes, moderately, no).
For each eligible sedated patient discharged from the PACU with a pain VRS 3 and a Ramsay score >3, 2 IV morphine-titrated patients discharged from the PACU with a pain VRS <3, irrespective of the Ramsay score, matched for gender, age (maximum difference of ±5 yr), weight (maximum difference of ±10% of body weight), and type of surgery were designated as part of a control group and investigated in an identical manner.
The demographic data, type and duration of surgery, the intraoperative sufentanil doses, total morphine doses administered in PACU, use of intraoperative ketamine, perioperative ketoprofen and of postoperative PCA or subcutaneous morphine, time in the PACU, total doses of PCA morphine requested during the 24 postoperative hours, frequency of nausea and vomiting in the PACU, the Ramsay score when discharged from the PACU, self-assessment of early and late postoperative pain, discomfort, and satisfaction were recorded 24 h postoperatively and compared.
The data are expressed as a mean (sd) when the variables were normally distributed, or a median (range) when the variables were not normally distributed. Continuous variables were analyzed using the Student’s t test or the Mann-Whitney U test, as appropriate. The Fisher’s exact method was used for categorical variables. All P values were two-tailed. P < 0.05 was required to exclude the null hypothesis. The statistical analysis was performed using Staview 5 software (Deltasoft, Meylan, France).
RESULTS
Of 285 patients admitted to the PACU during the study period, 26 patients with a Ramsay score >3 and a pain VRS 3 during morphine titration were studied. Fifty-two patients with a pain VRS <3 were used as controls. Surgical procedures conducted on the investigated patients, expressed as percentages, are reported in Table 1. Demographic, and intra- and postoperative anesthetic data are reported in Table 2. Statistical analysis confirmed that the control group (pain VRS <3) was adequately matched with the sedated group in pain (Ramsay score >3, pain VRS 3): the groups did not differ in demographic data, type and duration of surgery, doses of intraoperative sufentanil; patients receiving intraoperative ketamine and perioperative ketoprofen, and postoperative PCA or subcutaneous morphine in the ward; and episodes of nausea and vomiting. As expected, patients with Ramsey scores >3 and pain VRS 3 received more IV morphine in the PACU and had higher Ramsay scores when discharged from the PACU than patients in the control group. Sedated patients in pain spent more time in the PACU than did patients in the control group. Seven sedated patients in pain and 16 control patients were treated by PCA morphine. Sedated patients in pain requested the first bolus of morphine later than did control patients, but total doses of morphine requested during the 24 postoperative hours did not differ significantly between groups. The 24th hour postsurgery assessment demonstrated that patients who were discharged from the PACU highly sedated (Ramsay scores >3) and with a high pain score (VRS 3), more frequently experienced a memory of having had moderate-to-severe pain and discomfort after their operation (Table 3). Moreover, this difference in pain and discomfort persisted for 24 h after surgery (Table 3). Not surprisingly, patients sedated in pain in the PACU (Ramsay scores >3, pain VRS 3) were less satisfied with pain care provided during the first 24 postoperative hours than patients in the control group (all P values 0.001).
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DISCUSSION
Despite being sedated as assessed by Ramsay scores >3, patients discharged from the PACU with pain VRS 3, when verbally stimulated more frequently experienced moderate-to-severe early postoperative pain and discomfort and poor sleep the night after surgery than patients discharged from the PACU with a pain VRS <3 when investigated 24 h postoperatively. Pain persisted for at least 24 h postsurgery. Morphine-induced sedation did not suppress the memory of early postoperative painful circumstances. Reduced satisfaction with their postoperative care was also recorded.
Quality assurance programs include pain assessment in PACUs by nurses using unidimensional pain scales (1–4,6–8). Among the morphine-induced side effects, sedation, as assessed by a Ramsay score >3, was reported to occur in up to 60% of patients in the PACUs and is a common reason for discontinuing IV morphine administration (2,3). Twenty-five percent of patients sedated in PACUs (Ramsay score >3) was reported to have high pain scores as assessed on unidimensional pain scales when they awakened, although they did not spontaneously express pain (2). Postoperative sedation associated with high pain scores after IV morphine administration in PACUs has been confirmed using bispectral index monitoring (2).
The significance of postoperative sedation after IV morphine administration in PACUs is not clear (2,13). Significant sedation was observed before analgesia, after alfentanil administration alone in healthy volunteers submitted to electrical stimulation and thermal heat, thus suggesting that some patients could be sedated before analgesia after opioid administration (14). The residual effects of various drugs given as a premedication or intraoperatively may also interfere with or enhance the effects of IV morphine titration in PACUs (13). To our knowledge, morphine-induced sedation has not insured amnesia from painful postoperative discomfort, in contrast with pharmacologic sedation (5).
This investigation used methods for assessing pain that have been validated and have been alleged to reduce the risk of under- or over-reporting pain by PACU nurses (1,3,4,6–8,15). In this study, a verbal scale was used in the PACU because a visual scale is difficult to use in the postoperative period because of residual adverse effects of GA, including blurred vision, and psychomotor dysfunction (7). The verbal pain scale was demonstrated to correlate well with the visual scale in the postoperative period (7). All anesthetic procedures were conducted using the same drugs. Remifentanil, which can enhance postoperative hyperalgesia, was not administered to any patient (16). Ketamine administration prevents or reduces postoperative hyperalgesia, but the two groups did not differ in the number of patients receiving small doses of intraoperative ketamine (9). Also, the number of patients receiving intra- and postoperative ketoprofen was similar in both groups (10).
This study has clinical relevance. Many patients have a Ramsay score >3 during morphine titration in the PACU (2,3). When patients develop a Ramsey score >3 during morphine titration, its administration is commonly discontinued due to safety concerns, regardless of the pain score (2,3). A high percentage of patients with opioid-induced sedation had persistently high pain scores (VRS 3) in the PACU, and experienced a higher level of pain and discomfort during the initial 24-h postoperative period when compared with patients discharged from PACU with VRS pain scores <3 (2). Not surprisingly, patient satisfaction was lower in the highly sedated group in pain than in the control group. It is important to note that we studied patients who had different surgical procedures. Thus high pain scores were also recorded in sedated patients after minor surgical procedures such as thyroidectomy or lymph node removal, which do not consistently include extended tissue trauma and often do not require morphine administration in PACUs (17). Also, pain is considered a vital sign, and inadequately managed pain has been shown to diminish functional recovery (1,18). Thus, sedated patients with high pain scores must not be discharged from PACUs, and additional analgesic interventions devoid of sedative effects are recommended to decrease their pain scores (18).
The limitations of our study include the small sample size and, by design, the lack of randomization. In our opinion, low P values suggest that these limitations do not eliminate our conclusions. The assessment was intentionally limited to simple questions that could easily be asked at the bedside. We believe that the criteria investigated were relevant to a proper assessment of pain care.
Morphine rescue doses were not administered on the ward because a postoperative acute pain service, allowing pain reevaluation, was not available at night in our institution. Hydroxyzine, a long-acting sedative drug administered as a premedication, may have partly accounted for deep sedation in the present study (13). This does not exclude our findings that deep sedation in the PACU was not synonymous with the memory of adequate pain control. The subgroup of sedated patients in pain spent more time in the PACU than the control group, mainly for safety reasons. During the 24 postoperative hours, patients of both groups treated by subcutaneous morphine administration received the same doses of morphine by design. Among the subgroup of patients treated by PCA morphine, total morphine requirement did not differ significantly between groups during the 24 postoperative hours. However, sedated patients in pain required the first dose of morphine later than did the control patients, and therefore requested this identical dose of morphine during a shorter period. We believe that deep sedation is likely to have accounted for this delayed morphine requirement. Finally, we do not believe that awaking patients for pain assessment favored pain recall as a consequence of discontinuing sedation.
In conclusion, concern over opioid-related side effects limited morphine administration in the PACU and was likely to have caused under-treatment of postoperative pain. Sedated patients in pain in the PACU were likely to have had poor pain control for at least the first 24 postoperative hours, and less likely to be satisfied with the overall pain care provided during the first 24 postoperative hours.
ACKNOWLEDGMENTS
We thank the nursing staff in the PACU unit for their work on this study.
Footnotes
Accepted for publication June 18, 2007.
No conflict of interest has to be feared.
REFERENCES
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