Esther M. Pogatzki-Zahn

Effectiveness and safety of postoperative pain management: a survey of 18 925 consecutive patients between 1998 and 2006 (2nd revision): a database analysis of prospectively raised data†

BACKGROUND Approximately 30-80% of postoperative patients complain about moderate to severe post-surgical pain, indicating that postoperative pain treatment is still a problem. METHODS We analysed prospectively collected data on patients in a university hospital receiving systemic and epidural patient-controlled analgesia and continuous peripheral nerve block (CPNB) documented by the acute pain service team in a computer-based system. RESULTS Of 18 925 patients visited in the postoperative period between 1998 and 2006, 14 223 patients received patient-controlled epidural analgesia (PCEA), 1591 i.v. patient-controlled analgesia (IV-PCA), 1737 continuous brachial plexus block, and 1374 continuous femoral/sciatic nerve block. Mean dynamic and resting pain scores (VAS 0-100) were significantly lower for peripheral or neuroaxial regional analgesia compared with patient-controlled systemic opioid analgesia (P<0.05). The risk of a symptomatic spinal mass lesion including epidural haematoma (0.02%; 1:4741) or epidural abscess (0.014%; 1:7142) after PCEA was 1:2857 (0.04%). Neurological complications after CPNB occurred in two patients who received interscalene brachial plexus block. CONCLUSIONS We demonstrated that PCEA, IV-PCA, and CPNB are safe and efficient. Although all of these treatment strategies provide effective analgesia, PCEA and CPNB provided superior pain relief compared with IV-PCA. We demonstrated that serious complications of analgesic techniques are rare but possibly disastrous necessitating a close supervision by an acute pain service. We found a low rate of adverse effects including hypotension and motor impairment and a low incidence of epidural haematoma for thoracic PCEA compared with lumbar PCEA.

Efficacy and safety of paravertebral blocks in breast surgery: a meta-analysis of randomized controlled trials

BACKGROUND Thoracic paravertebral blocks (PVBs) are successfully performed for pain management after breast surgery. The aim of the present quantitative systematic review was to assess the efficacy and adverse events of PVB in women undergoing breast surgery. METHODS The systematic search, data extraction, critical appraisal, and pooled analysis were performed according to the PRISMA statement. The relative risk (RR), mean difference (MD), and their corresponding 95% confidence intervals (CIs) were calculated using the RevMan statistical software for dichotomous and continuous outcomes, respectively. Pain scores were converted to a scale ranging from 0 (no pain) to 10 (worst pain). RESULTS Fifteen randomized controlled trials (published between 1999 and 2009) including 877 patients met the inclusion criteria. There was a significant difference in worst postoperative pain scores between PVB and general anaesthesia (GA) at <2 h (MD: -2.68; 95% CI: -3.33 to -2.02; P<0.00001), 2-24 h (MD: -2.34; 95% CI: -2.42 to -1.12; P<0.00001), and 24-48 h (MD: -1.75; 95% CI: -3.19 to 0.31; P=0.02). Accordingly, lower pain scores were observed for combined PVB with GA compared with GA alone for <2 h (MD: -1.87; 95% CI: -2.53 to -1.21; P<0.00001), 2-24 h (MD: -2.21; 95% CI: -3.07 to -1.35; P<0.00001), and 24-48 h (MD: -1.80; 95% CI: -2.92 to 0.68; P=0.002). The RR for the reported adverse events (e.g. pneumothorax) was low. CONCLUSIONS There is considerable evidence that PVB in addition to GA or alone provide a better postoperative pain control with little adverse effects compared with other analgesic treatment strategies.

From preemptive to preventive analgesia.

Purpose of review Much effort has been taken to prove that a treatment initiated before surgery is more effective in reducing postoperative pain compared with the same intervention started after surgery. Clinical studies failed to demonstrate major clinical benefits of preemptive analgesia, however, and the results of recent systemic reviews are equivocal. The present review will discuss recent clinical as well as experimental evidence of preemptive analgesia and examine the implications of a preventive postoperative pain treatment. Recent findings Recent preclinical and clinical studies give strong evidence that neuronal hypersensitivity and nociception after incision is mainly maintained by the afferent barrage of sensitized nociceptors across the perioperative period. This is in contrast to pain states of other origin in which prolonged hypersensitivity is initiated during the injury. Therefore, not timing but duration and efficacy of an analgesic and antihyperalgesic intervention are most important for treating pain and hyperalgesia after surgery. Summary Extending a multimodal analgesic treatment into the postoperative period to prevent postoperative pain may be superior compared with preemptive analgesia. In the future, appropriate drug combinations, drug concentrations and duration of preventive strategies need to be determined to be most beneficial for the management of acute and chronic pain after surgery.

Procedure-specific risk factor analysis for the development of severe postoperative pain.

Background: Many studies have analyzed risk factors for the development of severe postoperative pain with contradictory results. To date, the association of risk factors with postoperative pain intensity among different surgical procedures has not been studied and compared. Methods: The authors selected precisely defined surgical groups (at least 150 patients each) from prospectively collected perioperative data from 105 German hospitals (2004–2010). The association of age, sex, and preoperative chronic pain intensity with worst postoperative pain intensity was studied with multiple linear and logistic regression analyses. Pooled data of the selected surgeries were studied with random-effect analysis. Results: Thirty surgical procedures with a total number of 22,963 patients were compared. In each surgical procedure, preoperative chronic pain intensity and younger age were associated with higher postoperative pain intensity. A linear decline of postoperative pain with age was found. Females reported more severe pain in 21 of 23 surgeries. Analysis of pooled surgical groups indicated that postoperative pain decreased by 0.28 points (95% CI, 0.26 to 0.31) on the numeric rating scale (0 to 10) per decade age increase and postoperative pain increased by 0.14 points (95% CI, 0.13 to 0.15) for each higher score on the preoperative chronic pain scale. Females reported 0.29 points (95% CI, 0.22 to 0.37) higher pain intensity. Conclusions: Independent of the type and extent of surgery, preoperative chronic pain and younger age were associated with higher postoperative pain. Females consistently reported slightly higher pain scores regardless of the type of surgery. The clinical significance of this small sex difference has to be analyzed in future studies.

Spinal administration of MK-801 and NBQX demonstrates NMDA-independent dorsal horn sensitization in incisional pain.

&NA; Surgery commonly causes pain and neural plasticity that are unique compared to other persistent pain problems. To more precisely study central sensitization and plasticity, we examined the role of ionotropic EAA receptors in dorsal horn neuron sensitization early after incision. Sensitization, in the form of increased background activity, increased mechanosensitivity or pinch receptive field expansion, was induced by plantar incision 1 h later in 30 neurons. (+)‐5‐Methyl‐10,11‐dihydro‐5H‐dibenzo(a,d)cyclohepten‐5,10‐imine (MK‐801) or 1 mM 1,2,3,4‐tetrahydro‐6‐nitro‐2,3‐dioxo[f]quinoxaline‐7‐sulfonamide (NBQX) was administered through a microdialysis fiber to block NMDA and nonNMDA EAA receptors, respectively. Dorsal horn neuron sensitization was reexamined 1 h later. Spinal administration of NBQX blocked AMPA‐induced excitation but did not affect excitation by NMDA. NBQX decreased background activity in the neurons that developed sustained increased activity after incision. The median decrease caused by NBQX was from 2.3 to 0.0 imp/s. Spinal administration of 5 mM MK‐801 blocked NMDA‐induced excitation but did not affect excitation by AMPA. The median change (from 2.6 to 1.1 imp/s) in background activity increased by incision was not significantly affected by MK‐801. The responses to mechanical stimuli were enhanced after incision in wide dynamic range (WDR) neurons. NBQX eliminated these responses but MK‐801 had no effect. The pinch receptive field (RF) expansion into uninjured areas of the paw and hindquarters occurred after incision. Only 1 of 13 neurons exhibited RF expansion after spinal NBQX administration; 9 of 12 neurons had RF expansion remaining after MK‐801. Thus, nonNMDA receptors are critical and NMDA‐independent factors influence the increased responsiveness of dorsal horn neurons that occur early after incision.

Is intraoperative dexmedetomidine a new option for postoperative pain treatment? A meta-analysis of randomized controlled trials

&NA; Adults treated with intraoperative dexmedetomidine infusion reported lower postoperative pain intensities and consumed less postoperative opioids compared with placebo. &NA; In the present meta‐analysis, we assessed the efficacy and safety of intravenous administration of dexmedetomidine (DEX) compared with placebo or opioids for acute postoperative pain treatment in adults undergoing surgery. The meta‐analysis was performed according to the preferred reporting items for systematic reviews and meta‐analyses (PRISMA) statement and the recommendations of the Cochrane Collaboration. Randomized controlled trials investigating perioperative administration of DEX were included. For dichotomous outcomes relative risks (RR; 95% confidence intervals [CI]) and for continuous outcomes mean differences (MD; 95% CI) were calculated. Twenty‐eight randomized controlled trials including 1420 patients were finally included. Patients treated with DEX reported lower postoperative pain intensity (MD1 h postoperatively: −1.59 U (numeric rating scale: 0 to 10) 95% CI: −2.37 to −0.82; P = .000001) and showed a lower postoperative opioid consumption (MD24 h postoperatively: −17.24 mg; 95% CI: −24.38 to −10.10; P = .00001) compared with placebo. Additionally, the DEX group showed a lower RR for opioid‐related adverse events (e.g. RRNausea (postanesthesia care unit): 0.66; 95% CI: 0.43 to 1.02; P = .06). The most common adverse event in patients treated with DEX was intraoperative bradycardia with a RR of 2.66 (RR: 2.66; 95% CI: 1.54 to 4.58; P = .0004) compared with placebo. There is evidence that DEX administration leads to lower postoperative pain, reduced opioid consumption, and a lower risk for opioid‐related adverse events. The comparison of DEX vs opioids for postoperative pain treatment is less clear due to limited data. The most common adverse event was intraoperative bradycardia after DEX administration. Therefore cautions in patients at risk are warranted, and large trials focusing on long‐ term outcomes after intraoperative DEX use are needed.

Chronic postsurgical pain in Europe: An observational study.

BACKGROUND Chronic postsurgical pain (CPSP) is an important clinical problem. Prospective studies of the incidence, characteristics and risk factors of CPSP are needed. OBJECTIVES The objective of this study is to evaluate the incidence and risk factors of CPSP. DESIGN A multicentre, prospective, observational trial. SETTING Twenty-one hospitals in 11 European countries. PATIENTS Three thousand one hundred and twenty patients undergoing surgery and enrolled in the European registry PAIN OUT. MAIN OUTCOME MEASURES Pain-related outcome was evaluated on the first postoperative day (D1) using a standardised pain outcome questionnaire. Review at 6 and 12 months via e-mail or telephonic interview used the Brief Pain Inventory (BPI) and the DN4 (Douleur Neuropathique four questions). Primary endpoint was the incidence of moderate to severe CPSP (numeric rating scale, NRS ≥3/10) at 12 months. RESULTS For 1044 and 889 patients, complete data were available at 6 and 12 months. At 12 months, the incidence of moderate to severe CPSP was 11.8% (95% CI 9.7 to 13.9) and of severe pain (NRS ≥6) 2.2% (95% CI 1.2 to 3.3). Signs of neuropathic pain were recorded in 35.4% (95% CI 23.9 to 48.3) and 57.1% (95% CI 30.7 to 83.4) of patients with moderate and severe CPSP, respectively. Functional impairment (BPI) at 6 and 12 months increased with the severity of CPSP (P < 0.01) and presence of neuropathic characteristics (P < 0.001). Multivariate analysis identified orthopaedic surgery, preoperative chronic pain and percentage of time in severe pain on D1 as risk factors. A 10% increase in percentage of time in severe pain was associated with a 30% increase of CPSP incidence at 12 months. CONCLUSION The collection of data on CPSP was feasible within the European registry PAIN OUT. The incidence of moderate to severe CPSP at 12 months was 11.8%. Functional impairment was associated with CPSP severity and neuropathic characteristics. Risk factors for CPSP in the present study were chronic preoperative pain, orthopaedic surgery and percentage of time in severe pain on D1. TRIAL REGISTRATION Clinicaltrials.gov identifier: NCT01467102.

Analysis of hyperalgesia time courses in humans after painful electrical high-frequency stimulation identifies a possible transition from early to late LTP-like pain plasticity

&NA; Electrical high‐frequency stimulation (HFS) of skin afferents elicits long‐term potentiation (LTP)‐like hyperalgesia in humans. Time courses were evaluated in the facilitating (homotopic) or facilitated (heterotopic) pathways to delineate the relative contributions of early or late LTP‐like pain plasticity. HFS in healthy subjects (n = 55) elicited highly significant pain increases to electrical stimuli via the conditioning electrode (to 145% of control, homotopic pain LTP) and to pinprick stimuli in adjacent skin (to 190% of control, secondary hyperalgesia). Individual time courses in subjects expressing a sufficient magnitude of hyperalgesia (>20% pain increase, n = 28) revealed similar half‐lives of homotopic pain LTP and secondary hyperalgesia of 6.9 h and 4.9 h (log10 mean 0.839 ± 0.395 and 0.687 ± 0.306) and times to full recovery of 48 h and 24 h (log10 mean 1.679 ± 0.790 and 1.373 ± 0.611). Time course and peak magnitudes were not correlated between (r = −0.19 to +0.21, NS), nor within both readout (r = 0.29 and 0.31, NS). In most subjects, time courses were consistent with early LTP1. Notably, in some subjects (10 of 28), estimated times to full recovery were much longer (>10 days), possibly indicating development of late LTP2‐like pain plasticity. Dynamic mechanical allodynia (only present in 16 of 55 subjects) lasted for a shorter time than secondary hyperalgesia. Three different readouts of nociceptive central sensitization suggest that brief intense nociceptive input elicits early LTP1 of pain sensation (based on posttranslational modifications), but susceptible subjects may already develop longer‐lasting late LTP2 (based on transcriptional modifications). These findings support the hypothesis that LTP may contribute to the development of persistent pain disorders. Homotopic pain LTP, secondary hyperalgesia, and dynamic mechanical allodynia after painful electrical high‐frequency stimulation are mostly LTP1‐like processes terminating within hours/1 day, but susceptible subjects may exhibit LTP2‐like pain plasticity lasting many days or weeks.

Efficacy and adverse effects of ketamine as an additive for paediatric caudal anaesthesia: a quantitative systematic review of randomized controlled trials

BACKGROUND The aim of this quantitative systematic review was to assess the efficacy and adverse effects of ketamine added to caudal local anaesthetics in comparison with local anaesthetics alone in children undergoing urological, lower abdominal, or lower limb surgery. METHODS The systematic search, data extraction, critical appraisal, and pooled data analysis were performed according to the PRISMA statement. All randomized controlled trials (RCTs) were included in this meta-analysis and relative risk (RR), mean difference (MD), and the corresponding 95% confidence intervals (CIs) were calculated using the Revman(®) statistical software for dichotomous and continuous outcomes. RESULTS Thirteen RCTs (published between 1991 and 2008) including 584 patients met the inclusion criteria. There was a significant longer time to first analgesic requirements in patients receiving ketamine in addition to a local anaesthetic compared with a local anaesthetic alone (MD: 5.60 h; 95% CI: 5.45-5.76; P<0.00001). There was a lower RR for the need of rescue analgesia in children receiving a caudal regional anaesthesia with ketamine in addition to local anaesthetics (RR: 0.71; 95% CI: 0.44-1.15; P=0.16). CONCLUSIONS Caudally administered ketamine, in addition to a local anaesthetic, provides prolonged postoperative analgesia with few adverse effects compared with local anaesthetics alone. There is a clear benefit of caudal ketamine, but the uncertainties about neurotoxicity relating to the dose of ketamine, single vs repeated doses and the childs age, still need to be clarified for use in clinical practice.

Efficacy and safety of intraoperative dexmedetomidine for acute postoperative pain in children: a meta-analysis of randomized controlled trials.

Aim of the current meta‐analysis was to assess the effects of intraoperative dexmedetomidine on postoperative pain, analgesic consumption, and adverse events in comparison with placebo or opioids in children undergoing surgery.