Whether preemptive analgesic interventions are more effective than conventional regimens in managing acute postoperative pain remains controversial. We systematically searched for randomized controlled trials that specifically compared preoperative analgesic interventions with similar postoperative analgesic interventions via the same route. The retrieved reports were stratified according to five types of analgesic interventions: epidural analgesia, local anesthetic wound infiltration, systemic N-methyl-d-aspartic acid (NMDA) receptor antagonists, systemic nonsteroidal antiinflammatory drugs (NSAIDs), and systemic opioids. The primary outcome measures analyzed were the pain intensity scores, supplemental analgesic consumption, and time to first analgesic consumption. Sixty-six studies with data from 3261 patients were analyzed. Data were combined by using a fixed-effect model, and the effect size index (ES) used was the standardized mean difference. When the data from all three outcome measures were combined, the ES was most pronounced for preemptive administration of epidural analgesia (ES, 0.38; 95% confidence interval [CI], 0.28-0.47), local anesthetic wound infiltration (ES, 0.29; 95% CI, 0.17-0.40), and NSAID administration (ES, 0.39; 95% CI, 0.27-0.48). Whereas preemptive epidural analgesia resulted in consistent improvements in all three outcome variables, preemptive local anesthetic wound infiltration and NSAID administration improved analgesic consumption and time to first rescue analgesic request, but not postoperative pain scores. The least proof of efficacy was found in the case of systemic NMDA antagonist (ES, 0.09; 95% CI, -0.03 to 0.22) and opioid (ES, -0.10; 95% CI, -0.26 to 0.07) administration, and the results remain equivocal.

The efficacy of preemptive analgesia for acute postoperative pain management: a meta-analysis.

Objective To identify and assess the impact of postoperative complications in patients with unrecognized or known obstructive sleep apnea syndrome (OSAS) undergoing hip replacement or knee replacement compared with control patients undergoing similar operations. Although OSAS is a risk factor for perioperative morbidity, data quantifying the magnitude of the problem in patients undergoing non-upper airway operations are limited. PATIENTS AND METHODS This retrospective, case-control study from a single academic medical institution included patients diagnosed as having OSAS between January 1995 and December 1998 and undergoing hip or knee replacement within 3 years before or anytime after their OSAS diagnosis. Patients with OSAS were subcategorized as having the diagnosis either before or after the surgery and also, regardless of time of diagnosis, by whether they were using continuous positive airway pressure (CPAP) prior to hospitalization. Matched controls were patients without OSAS undergoing the same operation. Interventions were defined specifically as administration of a particular treatment in the context of each complication, eg, supplemental oxygen, implementation of additional monitoring such as oximetry for hypoxemia, or transfer to the intensive care unit (ICU) for cardiac ischemia concerns. Postoperative complications were assessed for all patients in the different categories and included respiratory events such as hypoxemia, acute hypercapnia, and episodes of delirium. Serious complications were noted separately, including unplanned ICU days, reintubations, and cardiac events. The length of hospital stay was also tabulated. Results There were 101 patients with the diagnosis of OSAS in this study and 101 matched controls. Thirty-six patients had their joint replacement before OSAS was diagnosed, and 65 had surgery after OSAS was diagnosed. Of the latter 65 patients, only 33 were using CPAP at home preoperatively. Complications were noted in 39 patients (39%) in the OSAS group and 18 patients (18%) in the control group ( P =.001). Serious complications occurred in 24 patients (24%) in the OSAS group compared with 9 patients (9%) in the control group ( P =.004). Hospital stay was significantly longer for the OSAS patients at a mean ± SD of 6.8±2.8 days compared with 5.1±4.1 days for the control patients ( P Conclusion Adverse postoperative outcomes occurred at a higher rate in patients with a diagnosis of OSAS undergoing hip or knee replacement compared with a group of matched control patients.

https://www.mayoclinicproceedings.org/article/S0025-6196(11)62108-3/pdf

Postoperative complications in patients with obstructive sleep apnea syndrome undergoing hip or knee replacement: a case-control study

Objective
To report trends and characteristics of long-term opioid use for non-cancer pain.

Methods
CONSORT (CONsortium to Study Opioid Risks and Trends) includes adult enrollees of two health plans serving over 1 per cent of the US population. Using automated data, we constructed episodes of opioid use between 1997 and 2005. We estimated age–sex standardized rates of opioid use episodes beginning in each year (incident) and on-going in each year (prevalent), and the per cent change in rates annualized (PCA) over the 9-year period. Long-term episodes were defined as > 90 days with 120+ days supply or 10+ opioid prescriptions in a given year.

Results
Over the study period, incident long-term use increased from 8.5 to 12.1 per 1000 at Group Health (GH) (6.0% PCA), and 6.3 to 8.6 per 1000 at Kaiser Permanente of Northern California (KPNC) (5.5% PCA). Prevalent long-term use doubled from 23.9 to 46.8 per 1000 at GH (8.5% PCA), and 21.5 to 39.2 per 1000 at KPNC (8.1% PCA). Non-Schedule II opioids were the most commonly used opioid among patients engaged in long-term opioid therapy, particularly at KPNC. Long-term use of Schedule II opioids also increased substantially at both health plans. Among prevalent long-term users in 2005, 28.6% at GH and 30.2% at KPNC were also regular users of sedative hypnotics.

Conclusion
Long-term opioid therapy for non-cancer pain is increasingly prevalent, but the benefits and risks associated with such therapy are inadequately understood. Concurrent use of opioids and sedative-hypnotics was unexpectedly common and deserves further study. Copyright © 2009 John Wiley & Sons, Ltd.

/pdf/trends-in-long-term-opioid-therapy-for-chronic-non-cancer-2f3kl0fagt.pdf

Trends in long-term opioid therapy for chronic non-cancer pain.

In a rat model of morphine tolerance, we examined the hypotheses that thermal hyperalgesia to radiant heat develops in association with the development of morphine tolerance and that both the development and expression of thermal hyperalgesia in morphine-tolerant rats are mediated by central NMDA and non-NMDA receptors and subsequent protein kinase C (PKC) activation. Tolerance to the analgesic effect of morphine was developed in rats utilizing an intrathecal repeated treatment regimen. The development of morphine tolerance and thermal hyperalgesia was examined by employing the tail-flick test and paw- withdrawal test, respectively. Intrathecal MK 801 (an NMDA receptor antagonist), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; a non-NMDA receptor antagonist), or GM1 ganglioside (an intracellular PKC inhibitor) treatment was given to examine the effects of these agents on the development and expression of thermal hyperalgesia in morphine- tolerant rats. Tolerance to the analgesic effect of morphine was reliably developed in rats following once daily intrathecal (onto the lumbosacral spinal cord) injection of 10 micrograms of morphine sulfate for 8 consecutive days as demonstrated by the decreased analgesia following morphine administration on day 8 as compared to that on day 1. In association with the development of morphine tolerance, thermal hyperalgesia to radiant heat developed in these same rats. Paw- withdrawal latencies were reliably decreased in morphine-tolerant rats as compared to nontolerant (saline) controls when tested on day 8 before the last morphine treatment and on day 10 (i.e., 48 hr after the last morphine treatment). The coincident development of morphine tolerance and thermal hyperalgesia was potently prevented by intrathecal coadministration of morphine with MK 801 (10 nmol) or GM1 (160 nmol), and partially by CNQX (80 nmol). MK 801 (5, 10 nmol, not 2.5 nmol) and CNQX (80, 160 nmol, not 40 nmol), but not GM1 (160 nmol), also reliably reversed thermal hyperalgesia in rats rendered tolerant to morphine when tested 30 min after each drug treatment on day 10 (48 hr after the last morphine treatment). The data indicate that thermal hyperalgesia develops in association with the development of morphine tolerance and that the coactivation of central NMDA and non-NMDA receptors is crucial for both the development and expression of thermal hyperalgesia in morphine-tolerant rats. Furthermore, intracellular PKC activation plays a critical role in the development of thermal hyperalgesia in morphine-tolerant rats.(ABSTRACT TRUNCATED AT 400 WORDS)

https://www.jneurosci.org/content/jneuro/14/4/2301.full.pdf

Thermal hyperalgesia in association with the development of morphine tolerance in rats: roles of excitatory amino acid receptors and protein kinase C.

Study Objectives: Disturbed sleep is observed in association with acute and chronic pain, and some data suggest that disturbed and shortened sleep enhances pain. We report the first data showing, in healthy, pain-free, individuals, that modest reductions of sleep time and specific loss of rapid eye movement (REM) sleep produces hyperalgesia the following morning. Design: Two repeated-measures design protocols were conducted: (1) a sleep-loss protocol with 8 hours time-in-bed, 4 hours time-in-bed, and 0 hours time-in-bed conditions and (2) a REM sleep-loss protocol with 8 hours time-in-bed, 2 hours time-in-bed, REM deprivation, and non-REM yoked-control conditions. Setting: The studies were conducted in an academic hospital sleep laboratory. Participants: Healthy pain-free normal sleepers, 7 in the sleep-loss protocol and 6 in the REM sleep-loss protocol, participated. Measurements: Finger-withdrawal latency to a radiant heat stimulus tested at 10:30 AM and 2:30 PM and the Multiple Sleep Latency Test conducted at 10:00 AM, noon, 2:00 PM, and 4:00 PM were measured. Results: Finger-withdrawal latency was shortened by 25% after 4 hours of time in bed the previous night relative to 8 hours of time in bed (p <.05), and REM sleep deprivation relative to a non-REM yoked-control sleep-interruption condition shortened finger-withdrawal latency by 32% (p<.02). Conclusion: These studies showed that the loss of 4 hours of sleep and specific REM sleep loss are hyperalgesic the following day. These findings imply that pharmacologic treatments and clinical conditions that reduce sleep and REM sleep time may increase pain.

Sleep loss and REM sleep loss are hyperalgesic.

Characteristics of nocturnal sleep were investigated in six patients after anesthesia and cholecystectomy and in another six after anesthesia and gastroplasty. All night polysomnographic recordings were obtained while each patient slept in a private surgical ward room through two nights before and five or six nights after operation. Anesthesia included thiopental, N2O, isoflurane, and fentanyl. Postoperative analgesia was provided with parenteral morphine. Other aspects of care were routine. Nocturnal sleep was markedly disturbed after both surgical procedures. Throughout the operative night and subsequent one or two nights, sleep was highly fragmented with the usual recurring cycles of sleep stages completely disrupted. Slow wave sleep was suppressed and rapid eye movement (REM) sleep virtually eliminated. During the following 2-4 nights, as other aspects of sleep recovered, REM sleep reappeared and then increased to greater than the preoperative amount. This increased REM sleep was marked by a heavy density of eye movement activity along with frequent patient reports of unusually distressing dreams or vivid nightmares. It is concluded that anesthesia with upper abdominal surgery leads to a severe disruption of nocturnal sleep followed by the release of highly intense REM sleep about the middle of the first postoperative week.

Anesthesia with abdominal surgery leads to intense REM sleep during the first postoperative week.

Patients want safe and effective analgesia Our goal is to prevent postoperative pain in an efficient and cost effective manner For most patients, the pain can be managed using simple, non-invasive and inexpensive analgesic techniques Given the current economic climate, cost will become increasingly important There will be financial pressure to expand the scope of ambulatory surgery There will be pressure to discharge patients as soon as they are able to take oral medications Outpatient analgesia is the oldest and most widespread form of patient-controlled analgesia--We already have the knowledge and the analgesics necessary to prevent postoperative pain What we need now is logical, rational, and universal application of this information

https://link.springer.com/content/pdf/10.1007/BF03011550.pdf

The prevention of postoperative pain

Nocturnal sleep was studied in eight healthy young volunteers before and after isoflurane anesthesia. All night polysomnographic recordings were obtained for seven consecutive nights from approximately 2300 to 0700 h. On the morning after the third night each subject was anesthetized with isoflurane 1.1 MAC for approximately 3 h. The stages and indices of nocturnal sleep were calculated for each night of study according to standard criteria. The effects of anesthesia on nocturnal sleep were confined to the first postanesthetic night. Slow wave sleep (Stages 3 and 4) was moderately suppressed from 16 +/- 1% to 6 +/- 1%, and Stage 2 sleep reciprocally increased from 52 +/- 2% to 60 +/- 2% (mean +/- SEM, P less than 0.05). There were no detectable changes in the sleep onset latency, the total quantity of sleep, or the proportion of rapid eye movement (REM) sleep. Anesthesia was followed by daytime napping in six of the eight volunteers. Nocturnal sleep was similar in the subjects who napped and those who did not. It is concluded that anesthesia with isoflurane leads to a modest and a transient change in the architecture of nocturnal sleep.

Isoflurane anesthesia causes a transient alteration in nocturnal sleep.

Butscher describes a common-sense approach to pain management which is simple, safe and effective. A wide variety of national and international organization devoted to the management of pain have universally adopted these simple measures. Current guidelines advocate both regular dosing and rescue analgesia. These guidelines were produced by an army of international experts and have been available for a decade. Although the information is widely published, it is rarely adopted in clinical practice. It is any wonder that leaders in the field of pain management ask: "Is education enough?" "Will guidelines make a difference?" They continue to lament the "tragedy of needless pain" and in despair they have called for "national initiatives on pain." Bonica stated so elegantly, "for nearly 30 yr I have studied the reasons for inadequate management of postoperative pain, and they remain the same...inadequate or improper application of available information and therapies is certainly the most important reason for inadequate analgesia does not require futuristic high tech solutions. In fact, as the economic crunch continues we may find that we cannot afford some of these new, improved and more expensive techniques. If we can provide safe and effective analgesia for only pennies a day, this option cannot be ignored. The new way may be the old way.

/pdf/postoperative-pain-management-back-to-basics-3oo2hrdazo.pdf

Postoperative pain management--back to basics.

Inspiratory mechanical loads were applied to the airway continuously for 5 min in healthy young adult volunteers maintained in a near steady-state of halothane anesthesia 1.1 MAC. The loads, both flow resistive and elastic in nature, had been selected to reduce the first loaded tidal volume approximately 10, 30, or 50%—these being designated “small,” “medium,” and “large” loads, respectively. The actual magnitudes of resistive load were 8 ± 1, 21 ± 3, and 48 ± 6 cmH2O.1−1s, and of elastic load 6 ± 1, 18 ± 1, and 41 ± 5 cmH2O. 1−1(means ± SEM). All loads caused an immediate reduction of ventilation proportional to the size of the load. This was followed by a gradual recovery of ventilation toward control values over approximately 2 min and then nearly stable ventilation for the rest of the loading period. Respiratory frequency was unchanged throughout. At 5 min of loading, ventilation and Pco2 had been nearly steady for 3 min and O2 uptake and CO2 output at the airway were unchanged from control, suggesting the establishment of a near steady respiratory state. With the small and medium loads of both types, ventilation and Paco2 in this near steady-state were not detectably different from control. With the large loads, however, ventilation was significantly reduced and Paco2 slightly increased. The end-expiratory position of the chest wall and the relative contributions of the rib cage and abdomen-diaphragm to ventilation, as estimated by antereroposterior chest wall magnetometers, were not consistently altered by any load. The small elastic loads reduced the “effective” intrinsic elastance at the end of the loading period. Loading did not increase the ratio of dead space to tidal volume (VD/VT) or the alveolar-arterial oxygen tension difference (P(A-a)o2). It is concluded that in healthy young humans anesthetized with halothane, steady-state compensation for inspiratory flow-resistive loads up to about 21 cmH2O.1−1s and inspiratory elastic loads up to 18 cmH2O · 1−1is virtually complete. Ventilatory compensation for these loads is due to nonchemical mechanisms, which in the case of small elastic loads reduce intrinsic elastance and thereby improve the performance of the ventilatory pump.

Carol A. Moote

Papers

Anesthesia with abdominal surgery leads to intense REM sleep during the first postoperative week.

The prevention of postoperative pain

Isoflurane anesthesia causes a transient alteration in nocturnal sleep.

Postoperative pain management--back to basics.

Ventilatory compensation for continuous inspiratory resistive and elastic loads during halothane anesthesia in humans.