Peter K. 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.

Effect of Remote Ischemic Preconditioning on Kidney Injury Among High-Risk Patients Undergoing Cardiac Surgery: A Randomized Clinical Trial

IMPORTANCE No interventions have yet been identified to reduce the risk of acute kidney injury in the setting of cardiac surgery. OBJECTIVE To determine whether remote ischemic preconditioning reduces the rate and severity of acute kidney injury in patients undergoing cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS In this multicenter trial, we enrolled 240 patients at high risk for acute kidney injury, as identified by a Cleveland Clinic Foundation score of 6 or higher, between August 2013 and June 2014 at 4 hospitals in Germany. We randomized them to receive remote ischemic preconditioning or sham remote ischemic preconditioning (control). All patients completed follow-up 30 days after surgery and were analyzed according to the intention-to-treat principle. INTERVENTIONS Patients received either remote ischemic preconditioning (3 cycles of 5-minute ischemia and 5-minute reperfusion in one upper arm after induction of anesthesia) or sham remote ischemic preconditioning (control), both via blood pressure cuff inflation. MAIN OUTCOMES AND MEASURES The primary end point was the rate of acute kidney injury defined by Kidney Disease: Improving Global Outcomes criteria within the first 72 hours after cardiac surgery. Secondary end points included use of renal replacement therapy, duration of intensive care unit stay, occurrence of myocardial infarction and stroke, in-hospital and 30-day mortality, and change in acute kidney injury biomarkers. RESULTS Acute kidney injury was significantly reduced with remote ischemic preconditioning (45 of 120 patients [37.5%]) compared with control (63 of 120 patients [52.5%]; absolute risk reduction, 15%; 95% CI, 2.56%-27.44%; P = .02). Fewer patients receiving remote ischemic preconditioning received renal replacement therapy (7 [5.8%] vs 19 [15.8%]; absolute risk reduction, 10%; 95% CI, 2.25%-17.75%; P = .01), and remote ischemic preconditioning reduced intensive care unit stay (3 days [interquartile range, 2-5]) vs 4 days (interquartile range, 2-7) (P = .04). There was no significant effect of remote ischemic preconditioning on myocardial infarction, stroke, or mortality. Remote ischemic preconditioning significantly attenuated the release of urinary insulinlike growth factor-binding protein 7 and tissue inhibitor of metalloproteinases 2 after surgery (remote ischemic preconditioning, 0.36 vs control, 0.97 ng/mL2/1000; difference, 0.61; 95% CI, 0.27-0.86; P < .001). No adverse events were reported with remote ischemic preconditioning. CONCLUSIONS AND RELEVANCE Among high-risk patients undergoing cardiac surgery, remote ischemic preconditioning compared with no ischemic preconditioning significantly reduced the rate of acute kidney injury and use of renal replacement therapy. The observed reduction in the rate of acute kidney injury and the need for renal replacement warrants further investigation. TRIAL REGISTRATION German Clinical Trials Register Identifier: DRKS00005333.

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.

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.

Ultrasound compared with nerve stimulation guidance for peripheral nerve catheter placement: a meta-analysis of randomized controlled trials

BACKGROUND The aim of this meta-analysis was to compare the efficacy and safety of ultrasound (US) vs nerve stimulation (NS) guidance for peripheral nerve catheter placement. METHODS This meta-analysis was performed according to the PRISMA statement and the recommendations of the Cochrane Collaboration. For dichotomous outcomes relative risks [RRs; 95% confidence intervals (CIs)] were calculated, while for continuous outcomes, mean differences (MDs; 95% CI) were calculated. All statistical analyses were performed using the Revman® statistical software (Version 5.1). RESULTS Fifteen randomized controlled trials including 977 patients satisfied the inclusion criteria. Peripheral nerve catheters placed under US guidance showed a higher RR of 1.14 (95% CI: 1.02-1.27; P=0.02) for an overall successful block in comparison with NS. However, postoperative pain scales at movement (numeric rating scale: 0-10) were comparable between US- vs NS-guided peripheral nerve catheters 24 (MD: 0.08; 95% CI: -0.77 to 0.94; P=0.85) and 48 (MD: 1.0; 95% CI: -0.3 to 2.3; P=0.13) h after surgery. Patients receiving a US-guided peripheral nerve catheter had a lower RR of 0.13 (95% CI: 0.04-0.38; P=0.0002) for an accidental vascular puncture. CONCLUSIONS There is evidence that US-guided peripheral nerve catheters show a higher success rate and a lower risk for an accidental vascular puncture compared with NS guidance. However, this difference resulted only in marginally lower postoperative pain scores at rest. Nevertheless, these results were influenced by heterogeneity and should be interpreted with caution.

Efficacy and safety of clonidine as additive for caudal regional anesthesia: a quantitative systematic review of randomized controlled trials

Background:  Clonidine is still the most popular additive for caudal regional anesthesia. Aim of the present quantitative systematic review was to assess the efficacy and safety of the combined use of clonidine and local anesthetics in comparison with caudal local anesthetics alone.

Sex-related differences of patient-controlled epidural analgesia for postoperative pain.

Summary Pain in men and women treated with patient‐controlled epidural analgesia was almost equal; however, women showed lower total PCEA consumption that was influenced by BMI and vomiting. ABSTRACT Gender differences in pain modulation are evident but data are rare with regard to perioperative regional analgesia. The aim of the present analysis was to assess gender‐related differences in pain ratings, analgesic consumption, and adverse events in a large group of patients treated with patient‐controlled epidural analgesia (PCEA) after major surgery. Data from 14,988 adult patients (6506 women; 8482 men) receiving a PCEA between January 1998 and December 2009 were examined. Demographic data and postoperative measurements assessed by the Acute Pain Service, including total PCEA consumption, pain scores, and complications, were analyzed by using PASW Statistics (18.0; SPSS Inc, Chicago, IL, USA). Beyond standard descriptive analyses, gender‐related differences were investigated using a stepwise multivariate analysis of variances. Postoperative pain scores during rest and movement were almost equal between men and women. However, women showed lower total PCEA consumption consistently throughout the 5‐day observation period (relative reduction by 1.7%–10.2% compared to men; P = 0.00). Total PCEA consumption did not interact with surgical site (abdomen, thorax, extremity) (P = 0.379) or age (<50, 50–75, >75 years; P = 0.330), but was influenced by body mass index (P = 0.017) and vomiting (P = 0.011). Furthermore, motor blockade was greater in females compared to males (P = 0.000). In patients treated with PCEA, gender differences in numeric rating scale scores exist but are not clinically relevant. However, reduced total PCEA consumption in women might be a consequence of an increased incidence of motor blockade and vomiting; the latter point towards an opioid‐free PCEA solution in female patients at high risk for vomiting.

Monitoring heart rate variability to assess experimentally induced pain using the analgesia nociception index: A randomised volunteer study.

BACKGROUND Pain assessment using a numerical rating scale (NRS) is considered good clinical practice, but objective assessment in noncommunicating patients is still a challenge. A potential solution is to monitor changes in heart rate variability transformed into the analgesia nociception index (ANI), that offers a noninvasive means of pain quantification. OBJECTIVES The aim was to measure magnitudes, descending slopes and time courses of ANI following expected and unexpected painful, nonpainful and sham experimental stimuli and compare these with pain intensity as assessed by NRS in conscious human volunteers. We expected a negative correlation between ANI and NRS after painful stimuli. DESIGN Randomised stimuli and placebo-controlled, single-blinded study. SETTING Experimental pain simulation laboratory, Bochum, Germany. PARTICIPANTS Twenty healthy male students, (mean ± standard deviation; 24.2 ± 1.9 years) recruited via local advertising, were consecutively included. INTERVENTION ANI values were continuously recorded. After resting, four stimuli were applied in a random order on the right forearm (unexpected and expected electrical pain, expected nonpainful and sham stimuli). Blinded volunteers were asked to rate all four stimuli on NRS. MAIN OUTCOME MEASURES ANI means (0–100), amplitudes, maxima, minima and slopes with NRS pain intensity scores (0–10). RESULTS Resting alert volunteers showed ANI values of 82.05 ± 10.71. ANI decreased after a random stimulus (maximal decrease of 25.0 ± 7.3%), but different kinds of stimuli evoked similar results. NRS scores (median; interquartiles) were significantly (P = 0.008) higher after expected (5.25; 3.5–6.75) compared with unexpected (4.50; 3.0–5.0) pain stimuli. No correlation was found between ANI and NRS. CONCLUSION ANI did not allow a differentiation of painful, nonpainful or sham stimuli in alert volunteers. Therefore, ANI does not exclusively detect nociception, but may be modified by stress and emotion. Thus, we conclude that ANI is not a specific, robust measure for assessment of pain intensity.