Plasmapheresis as therapeutic option in a 16-year-old with EVALI: A case report.

Since 2019 when a cluster of cases with acute respiratory distress syndrome (ARDS) associated with e-cigarettes in the United States was reported, there have been increasing numbers of reports. Electronic-cigarette or Vaping Use-associated Lung Injury (EVALI) represents a recent entity of respiratory clinical syndromes, primarily in young adults. We report a previously healthy 16-year-old boy who developed severe ARDS following a brief nonspecific prodromal phase after excessive consumption of e-cigarettes. Despite maximum intensive care therapy, including several weeks of venovenous extracorporeal membrane oxygenation, plasmapheresis and repeated administration of immunoglobulins seemed the only way to achieve therapeutic success. Although many case reports have been published, to our knowledge, there are none to date on the therapeutic use of plasmaphoresis in severe EVALI. This case highlights the clinical features of EVALI and the diagnostic dilemma that can arise with EVALI occurring against the background of an expired SARS-CoV-2 infection, with a paediatric inflammatory syndrome (PIMS) as differential diagnosis. EVALI is a diagnosis of exclusion, and the medical history of vaping and e-cigarette use can provide valuable clues. Ethical approval for this case report (protocol number 23-145 RS) was provided by the Ethical Committee of the Department of Medicine, Philipps-Universität Marburg, Germany on 13th of June 2023. Written informed consent to publish this case and the associated images was obtained from the patient and his mother.

Nominal logistic regression analysis of variables determining needle visibility in ultrasound images - a full factorial cadaver study.

BACKGROUND: Needle visualization is essential to avoid vascular puncture and nerve injury in ultrasound-guided regional anesthesia. Several factors that statistically influence needle visibility have been described but the dimensions of their individual impact remain unclear. This study aimed to quantify the impact of various independent factors on ultrasound needle visibility. METHODS: A total of 1500 ultrasound videos of in-plane needle insertions were obtained in embalmed cadavers with ten different commercially available echogenic and non-echogenic needles at different insertion angles and bevel orientations in a full factorial study design. The visibility of needle tip and shaft were rated as "good" or "poor" visibility. Nominal logistic regression analyses were calculated for the visibility of the needle tip and shaft. RESULTS: SonoPlex Stim Sprotte, SonoTAP Facet (needle tip and shaft) and Spinostar PencilPoint (needle tip)), insertion angle and bevel orientation were associated with good ultrasound visibility, reaching statistical significance (p < 0.05). The range of the effect on the log-odds scale for needle tip visibility was largest for the insertion angle with 6.33, followed by the tissue condition (3.76), bevel orientation (1.45) and the needle types (1.25). Regarding the needle shaft visibility, the largest effect range was observed with the insertion angle (7.36), followed by the tissue conditions with 3.96, needle type (1.86) and bevel orientation (0.95). CONCLUSION: In-plane needle visibility in ultrasound images depends mainly on the insertion angle, as expected. This is closely followed by the tissue condition, which is a factor related to the patient, thus cannot be altered to improve needle visibility. In the dimensions of the log-odds scale, the choice of a specific needle is far less important towards achieving a good visualization, whereas optimizing the bevel orientation can have a larger impact than the needle choice. Concluding from the relative dimensions of factors that determine needle visibility in this model, the importance of needles with echogenic features may be overrated.

[Perioperative pain therapy in minimally invasive thoracic surgery]. / Perioperative Schmerztherapie bei minimal-invasiver Thoraxchirurgie.

Thoracic surgery is often associated with severe postoperative pain levels. Even though these are less pronounced in thoracoscopic approaches, mechanical irritation, compression or injury of intercostal nerves and placement of chest tubes can cause pain levels, which must be treated. An adequate pain therapy in thoracic surgery is essential as insufficient inspiration due to inadequate analgesia may result in postoperative complications. Epidural anesthesia was considered the gold standard in thoracotomy for a long time. For video-assisted thoracoscopy, however, it is sometimes no longer recommended due to its benefit-risk ratio. Alternative thoracic blocks are the paravertebral block, the erector spinae plane block and the serratus anterior block, for which research has found heterogeneous results.This article summarizes the current recommendations for perioperative management of thoracoscopic surgery and gives an overview of the PROSPECT recommendations as well as the current Association of the Scientific Medical Societies in Germany (AWMF) guidelines for perioperative and postoperative pain therapy. In particular, individual regional anesthesia techniques and their current evidence are reviewed.

Rebound pain and postoperative pain profile following brachial plexus block compared to general anaesthesia-An observational study.

BACKGROUND: Regional anaesthesia has the benefit of reducing the need for systemic analgesia and therefore, potentially reducing undesired side effects. With the end of the sensory nerve block however, many patients report severe pain that requires therapy with opioids and often compromise the initial opioid sparing effect. This study aimed to characterise the postoperative pain profile and the phenomenon of rebound pain after axillary brachial plexus anaesthesia (RA) compared to general anaesthesia (GA). DESIGN: Single-centre observational, stratified cohort study. SETTING: The study was conducted at University Hospital Marburg from May 2020 until September 2022. PARTICIPANTS: One hundred thirty-two patients receiving elective hand and forearm surgery were enrolled in this study. INTERVENTIONS: Group RA received ultrasound-guided brachial plexus anaesthesia via the axillary approach with 30 mL of prilocaine 1% and 10 mL ropivacaine 0.2%. Group GA received balanced or total intravenous general anaesthesia. MAIN OUTCOME MEASURES: Primary endpoint were integrated pain scores (IPS) within 24 h postoperatively. Secondary endpoints were pain scores (NRS 0-10), morphine equivalents, patient satisfaction, quality of recovery and opioid-related side effects. RESULTS: One hundred thirty-two patients were analysed of which 66 patients received brachial plexus block and 66 patients received general anaesthesia. Following RA significantly lower IPS were seen directly after surgery (p < .001) and during the post-anaesthesia care unit interval (p < .001) but equalised after 3 h at the ward. No overshoot in pain scores or increased opioid consumption could be detected. Patient satisfaction and postoperative recovery were comparable between both groups. CONCLUSION: The IPS and NRS was initially lower in the RA group, increased with fading of the block until equal to the GA group and equal thereafter. Although various definitions of rebound pain were met during this phase, the opioid sparing effect of regional anaesthesia was not counteracted by it. The incidence of episodes with uncontrolled, severe pain did not differ between groups. We found no clinical implications of rebound pain in this setting, since the RA group did not show higher pain scores than the GA group at any time point. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00021764).

Changes in the degree of substitution of HES in vivo and their influence on methods for determining HES concentrations in plasma.

OBJECTIVE: The degree of substitution (DS) of HES describes the average proportion of substituted glucose molecules in a starch molecule. Although no quantitative studies of the in vivo behavior of the DS have been conducted so far, most pharmacokinetic studies to date have measured HES concentrations using the enzymatic method. This method assumes that at any point in time after an infusion, the DS in a serum remains constant and is identical to the DS in the infused solution. In the present study, we examined the changes in the DS of HES 130/0.42 in vivo in an animal model and compared two methods of measuring HES concentrations in plasma (the enzymatic and the o-Toluidine method). METHODOLOGY: We randomized 22 pigs into 2 groups. After induction of anesthesia, the pigs received 500 ml or 1000 ml of HES 130/0.42 (Tetraspan®). The DS was measured directly after the infusion, then after 30, 60, 120 and 240 minutes. In determining the DS, the hydroxyethyl starch was extracted from the plasma and hydrolyzed with hydrochloric acid to form non-substituted glucose and hydroxyethyl glucose. Subsequently, the concentration of free unsubstituted glucose was determined enzymatically and the total concentration of all (i.e., substituted and unsubstituted) glucose molecules was determined using the o-Toluidine method. From this, the concentration of the substituted glucose (hydroxyethyl glucose) and the DS could be calculated. In addition, the HES concentration was measured first in vitro and then in vivo at any point after the infusion by both the enzymatic method and the o-Toluidine method. RESULTS: The DS increased significantly directly after the infusion from 0.42 to 0.53 (for 500ml) or to 0.50 (for 1000ml); 4 hours later this had further increased to 0.55 and 0.54, respectively (p <0.0001). The HES concentration in vitro showed no significant difference (p = 0.17) when determined with the enzymatic and the o-Toluidine method. In contrast, the serum concentrations in vivo displayed significant differences (p<0.0001) between the two measurement methods. Immediately after the infusion of 500ml HES, the concentration measured with the o-Toluidine method was 31% higher than the one measured with the enzymatic method; 4 hours later, this discrepancy was still at 25%. For 1000 ml HES, the differences amounted to 16% and 25%, respectively. CONCLUSION: The DS of HES in vivo increases significantly over time. As a result, an HES concentration measured with the enzymatic method in vivo will be significantly lower than the same concentration determined with the o-Toluidine method. In future pharmacokinetic studies, HES concentrations should be measured using a method that takes into account changes in the DS in vivo.

Pharmacologic interventions for the therapy of postanesthetic shivering in adults: a systematic review and network meta-analysis.

INTRODUCTION: Shivering is a common side effect after general anesthesia. Risk factors are hypothermia, young age and postoperative pain. Severe complications of shivering are rare but can occur due to increased oxygen consumption. Previous systematic reviews are outdated and have summarized the evidence on the topic using only pairwise comparisons. The objective of this manuscript was a quantitative synthesis of evidence on pharmacological interventions to treat postanesthetic shivering. EVIDENCE ACQUSITION: Systematic review and frequentist network meta-analysis using the R package netmeta. Endpoints were the risk ratio (RR) of persistent shivering at one, five and 10 minutes after treatment with saline/placebo as the comparator. Data were retrieved from Medline, Embase, Central and Web of Science up to January 2022. Eligibility criteria were: randomized, controlled, and blinded trials comparing pharmacological interventions to treat shivering after general anesthesia. Studies on shivering during or after any type of regional anesthesia were excluded as well as sedated patients after cardiac surgery. EVIDENCE SYNTHESIS: Thirty-two trials were eligible for data synthesis, including 28 pharmacological interventions. The largest network included 1431 patients. The network geometry was two-centered with most comparisons linked to saline/placebo or pethidine. The best interventions were after one minute: doxapram 2 mg/kg, tramadol 2 mg/kg and nefopam 10 mg, after 5 minutes: tramadol 2 mg/kg, nefopam 10 mg and clonidine 150 µg and after 10 minutes: nefopam 10 mg, methylphenidate 20 mg and tramadol 1 mg/kg, all reaching statistical significance. Pethidine 25 mg and clonidine 75 µg also performed well and with statistical significance in all networks. CONCLUSIONS: Nefopam, tramadol, pethidine and clonidine are the most effective treatments to stop postanesthetic shivering. The efficacy of doxapram is uncertain since different doses showed contradictory effects and the evidence for methylphenidate is based on a single comparison in only one network. Furthermore, both lack data on side effects. Further studies are needed to clarify the efficacy of dexmedetomidine to treat postanesthetic shivering.

Spinal anesthesia in ambulatory surgery.

Spinal anesthesia is a safe alternative to general anesthesia but remains underrepresented in the ambulatory setting. Most concerns relate to low flexibility of spinal anesthesia duration and the management of urinary retention in the outpatient setting. This review focuses on the characterization and safety of the local anesthetics that are available to adapt spinal anesthesia very flexibly to the needs of ambulatory surgery. Furthermore, recent studies on the management of postoperative urinary retention provide evidence for safe, but report wider discharge criteria and much lower hospital admission rates. With the local anesthetics that have current approval for usage in spinal anesthesia, most requirements for ambulatory surgeries can be met. The reported evidence on local anesthetics without approval supports clinically established off-label use and can improve the results even further.

The effect of adjuvants added to local anaesthetics for single-injection upper extremity peripheral regional anaesthesia: A systematic review with network meta-analysis of randomised trials.

BACKGROUND: Peripheral regional anaesthesia is frequently used for upper extremity surgery. To prolong the duration of analgesia, adjuvants can be added to single-injection local anaesthetics. Despite attempts to compare several adjuvants in pairwise meta-analyses, a comprehensive comparison is still missing. OBJECTIVE: The objective of this network meta-analysis was to determine the effectiveness of adjuvants in upper extremity peripheral nerve blocks. DESIGN: A systematic review of randomised controlled trials with network meta-analyses. DATA SOURCES: A literature search in Embase, CENTRAL, MEDLINE and Web of Science was performed up to March 2023. ELIGIBILITY CRITERIA: Randomised trials comparing different adjuvants injected perineurally in peripheral upper extremity nerve blocks were eligible. Frequentist network meta-analysis was conducted using a random effects model with physiological saline as the comparator. The primary endpoint was the ratio of means (ROM) of the duration of analgesia. RESULTS: The review included 242 randomised controlled trials with a total of 17 391 patients. Twenty-eight adjuvants were compared in the largest networks. Most network estimations consisted of a high proportion of direct evidence. Fourteen adjuvants increased the duration of analgesia significantly by the following factors, ROM [95% confidence interval (CI)]: dexamethasone 1.95 (1.79 to 2.13), buprenorphine 1.83 (1.51 to 2.24), butorphanol 1.84 (1.41 to 2.39), potassium chloride 1.89 (1.15 to 3.11), dexmedetomidine 1.70 (1.59 to 1.81), sufentanil 1.70 (1.27 to 2.29), ketorolac 1.68 (1.24 to 2.27), midazolam 1.55 (1.24 to 1.94), tramadol 1.52 (1.32 to 1.75), nalbuphine 1.50 (1.30 to 1.72), morphine 1.43 (1.09 to 1.88), magnesium sulfate 1.42 (1.20 to 1.67), clonidine 1.36 (1.24 to 1.50) and fentanyl 1.23 (1.08 to 1.40). Inconsistency in network meta-analysis was substantial. Overall side effect rates were low with all adjuvants. CONCLUSION: The best interventions to prolong the duration of analgesia were dexamethasone, followed by dexmedetomidine, opioids, electrolytes, ketorolac and midazolam. There are general concerns about the quality of underlying studies and the risk of publication bias. TRIAL REGISTRATION: PROSPERO 2018 CRD42018115722.

Risk factors and protective factors of acute postoperative pain: an observational study at a German university hospital with cross-sectional and longitudinal inpatient data.

OBJECTIVES: Surgical fear is one of the most important psychological risk factors for postoperative pain, but less is known about the contribution of protective factors. This study investigated somatic and psychological risk and resilience factors of postoperative pain and validated the German version of the Surgical Fear Questionnaire (SFQ). SETTING: University Hospital of Marburg, Germany. DESIGN: Single-centre observational study and cross-sectional validation study. PARTICIPANTS: Data for validating the SFQ were obtained from a cross-sectional observational study (N=198, mean age 43.6 years, 58.8% female) with persons undergoing different kinds of elective surgery. A sample of N=196 (mean age 43.0 years, 45.4% female) undergoing elective (orthopaedic) surgery was analysed to investigate somatic and psychological predictors of relevant acute postsurgical pain (APSP). OUTCOME MEASURES: Participants completed preoperative and postoperative assessments at postoperative days 1, 2 and 7. Presurgical pain, age, gender, pain expectation, surgical setting, physical status, anaesthesia, surgical fear, pain catastrophising, depression, optimism and self-efficacy were examined as predictors. RESULTS: Confirmatory factor analysis confirmed the original two-factor structure of the SFQ. Correlation analyses indicated good convergent and divergent validity. Internal consistency (Cronbach's α) was between 0.85 and 0.89. Blockwise logistic regression analyses for the risk of APSP revealed outpatient setting, higher preoperative pain, younger age, more surgical fear and low dispositional optimism as significant predictors. CONCLUSIONS: The German SFQ is a valid, reliable and economical instrument with which the important psychological predictor surgical fear can be assessed. Modifiable factors that increase the risk of postoperative pain were higher pain intensity before surgery and being fearful about negative consequences of the surgery whereas positive expectations seem to buffer against postsurgical pain. TRIAL REGISTRATION NUMBERS: DRKS00021764 and DRKS00021766.

Risk assessment for major adverse cardiovascular events after noncardiac surgery using self-reported functional capacity: international prospective cohort study.

BACKGROUND: Guidelines endorse self-reported functional capacity for preoperative cardiovascular assessment, although evidence for its predictive value is inconsistent. We hypothesised that self-reported effort tolerance improves prediction of major adverse cardiovascular events (MACEs) after noncardiac surgery. METHODS: This is an international prospective cohort study (June 2017 to April 2020) in patients undergoing elective noncardiac surgery at elevated cardiovascular risk. Exposures were (i) questionnaire-estimated effort tolerance in metabolic equivalents (METs), (ii) number of floors climbed without resting, (iii) self-perceived cardiopulmonary fitness compared with peers, and (iv) level of regularly performed physical activity. The primary endpoint was in-hospital MACE consisting of cardiovascular mortality, non-fatal cardiac arrest, acute myocardial infarction, stroke, and congestive heart failure requiring transfer to a higher unit of care or resulting in a prolongation of stay on ICU/intermediate care (≥24 h). Mixed-effects logistic regression models were calculated. RESULTS: In this study, 274 (1.8%) of 15 406 patients experienced MACE. Loss of follow-up was 2%. All self-reported functional capacity measures were independently associated with MACE but did not improve discrimination (area under the curve of receiver operating characteristic [ROC AUC]) over an internal clinical risk model (ROC AUCbaseline 0.74 [0.71-0.77], ROC AUCbaseline+4METs 0.74 [0.71-0.77], ROC AUCbaseline+floors climbed 0.75 [0.71-0.78], AUCbaseline+fitnessvspeers 0.74 [0.71-0.77], and AUCbaseline+physical activity 0.75 [0.72-0.78]). CONCLUSIONS: Assessment of self-reported functional capacity expressed in METs or using the other measures assessed here did not improve prognostic accuracy compared with clinical risk factors. Caution is needed in the use of self-reported functional capacity to guide clinical decisions resulting from risk assessment in patients undergoing noncardiac surgery. CLINICAL TRIAL REGISTRATION: NCT03016936.

[Symptom control in palliative care (excluding pain therapy)]. / Symptomkontrolle in der Palliativmedizin (ohne Schmerztherapie).

In the palliative phase of disease, patients often suffer from a variety of distressing symptoms. Often, treatment is difficult because several problems exist at the same time and the necessary medications can cause side effects that require treatment. This article addresses important symptoms - other than pain - and provides treatment recommendations based on current literature.

Biomarker-guided intervention to prevent acute kidney injury after major surgery (BigpAK-2 trial): study protocol for an international, prospective, randomised controlled multicentre trial.

INTRODUCTION: Previous studies demonstrated that the implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guideline-based bundle, consisting of different supportive measures in patients at high risk for acute kidney injury (AKI), might reduce rate and severity of AKI after surgery. However, the effects of the care bundle in broader population of patients undergoing surgery require confirmation. METHODS AND ANALYSIS: The BigpAK-2 trial is an international, randomised, controlled, multicentre trial. The trial aims to enrol 1302 patients undergoing major surgery who are subsequently admitted to the intensive care or high dependency unit and are at high-risk for postoperative AKI as identified by urinary biomarkers (tissue inhibitor of metalloproteinases 2*insulin like growth factor binding protein 7 (TIMP-2)*IGFBP7)). Eligible patients will be randomised to receive either standard of care (control) or a KDIGO-based AKI care bundle (intervention). The primary endpoint is the incidence of moderate or severe AKI (stage 2 or 3) within 72 hours after surgery, according to the KDIGO 2012 criteria. Secondary endpoints include adherence to the KDIGO care bundle, occurrence and severity of any stage of AKI, change in biomarker values during 12 hours after initial measurement of (TIMP-2)*(IGFBP7), number of free days of mechanical ventilation and vasopressors, need for renal replacement therapy (RRT), duration of RRT, renal recovery, 30-day and 60-day mortality, intensive care unit length-of-stay and hospital length-of-stay and major adverse kidney events. An add-on study will investigate blood and urine samples from recruited patients for immunological functions and kidney damage. ETHICS AND DISSEMINATION: The BigpAK-2 trial was approved by the Ethics Committee of the Medical Faculty of the University of Münster and subsequently by the corresponding Ethics Committee of the participating sites. A study amendment was approved subsequently. In the UK, the trial was adopted as an NIHR portfolio study. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and will guide patient care and further research. TRIAL REGISTRATION NUMBER: NCT04647396.

[Pain Management in Palliative Care]. / Schmerztherapie in der Palliativmedizin.

Patients in the palliative phase of a disease often suffer from pain, which leads to a significant reduction in quality of life. Since in most cases there is a progression rather than an improvement of the disease over time, pain therapy must also be dynamically adapted. Due to accompanying symptoms and the physical burden of the disease, treatment of pain is often difficult. In the palliative situation, pain should not only be understood as an excitation of nociceptors but is rather also an expression of mental stress. In this article, we would like to give an overview of the available drugs, application methods and alternative treatment options. Specifically, the article is divided into the following subsections: non-opioid analgesics, opioids, co-analgesics, patient-controlled analgesia procedures, neuraxial and peripheral regional anesthesia procedures, neurolysis, supportive therapies and palliative sedation. Thus, when treating palliative patients, the focus should not only be on the one symptom of pain, but, in the sense of the bio-psycho-social model, a multimodal oriented treatment of the patient with all his symptoms, also including his relatives, must be carried out.

Quantification of exhaled propofol is not feasible during single-lung ventilation using double-lumen tubes: A multicenter prospective observational trial.

BACKGROUND: Volatile propofol can be measured in exhaled air and correlates to plasma concentrations with a time delay. However, the effect of single-lung ventilation on exhaled propofol is unclear. Therefore, our goal was to evaluate exhaled propofol concentrations during single-lung compared to double-lung ventilation using double-lumen tubes. METHODS: In a first step, we quantified adhesion of volatile propofol to the inner surface of double-lumen tubes during double- and single-lumen ventilation in vitro. In a second step, we enrolled 30 patients scheduled for lung surgery in two study centers. Anesthesia was provided with propofol and remifentanil. We utilized left-sided double-lumen tubes to separately ventilate each lung. Exhaled propofol concentrations were measured at 1-min intervals and plasma for propofol analyses was sampled every 20 min. To eliminate the influence of dosing on volatile propofol concentration, exhalation rate was normalized to plasma concentration. RESULTS: In-vitro ventilation of double-lumen tubes resulted in increasing propofol concentrations at the distal end of the tube over time. In vitro clamping the bronchial lumen led to an even more pronounced increase (Δ AUC +62%) in propofol gas concentration over time. Normalized propofol exhalation during lung surgery was 31% higher during single-lung compared to double-lung ventilation. CONCLUSION: During single-lung ventilation, propofol concentration in exhaled air, in contrast to our expectations, increased by approximately one third. However, this observation might not be affected by change in perfusion-ventilation during single-lung ventilation but rather arises from reduced propofol absorption on the inner surface area of the double-lumen tube. Thus, it is only possible to utilize exhaled propofol concentration to a limited extent during single-lung ventilation. REGISTRATION OF CLINICAL TRIAL: DRKS-ID DRKS00014788 (www.drks.de).

Pulmonary inflammatory response and immunomodulation to multiple trauma and hemorrhagic shock in pigs.

BACKGROUND: Patients suffering from severe trauma experience substantial immunological stress. Lung injury is a known risk factor for the development of posttraumatic complications, but information on the long-term course of the pulmonary inflammatory response and treatment with mild hypothermia are scarce. AIM: To investigate the pulmonary inflammatory response to multiple trauma and hemorrhagic shock in a porcine model of combined trauma and to assess the immunomodulatory properties of mild hypothermia. METHODS: Following induction of trauma (blunt chest trauma, liver laceration, tibia fracture), two degrees of hemorrhagic shock (45 and 50%) over 90 (n = 30) and 120 min. (n = 20) were induced. Animals were randomized to hypothermia (33°C) or normothermia (38°C). We evaluated bronchoalveolar lavage (BAL) fluid and tissue levels of cytokines and investigated changes in microRNA- and gene-expression as well as tissue apoptosis. RESULTS: We observed a significant induction of Interleukin (IL) 1ß, IL-6, IL-8, and Cyclooxygenase-2 mRNA in lung tissue. Likewise, an increased IL-6 protein concentration could be detected in BAL-fluid, with a slight decrease of IL-6 protein in animals treated with hypothermia. Lower IL-10 protein levels in normothermia and higher IL-10 protein concentrations in hypothermia accompanied this trend. Tissue apoptosis increased after trauma. However, intervention with hypothermia did not result in a meaningful reduction of pro-inflammatory biomarkers or tissue apoptosis. CONCLUSION: We observed signs of a time-dependent pulmonary inflammation and apoptosis at the site of severe trauma, and to a lower extent in the trauma-distant lung. Intervention with mild hypothermia had no considerable effect during 48 hours following trauma.

Equianalgesic potency ratios of opioids used in patient-controlled analgesia: A network meta-analysis.

OBJECTIVE: To determine equianalgesic potency ratios for opioids with an -evidence-based approach without the use of pre-existing potency tables. DESIGN: Frequentist network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing opioids in patient-controlled analgesia (PCA). SETTING: A systematic review. DATA SOURCES: A systematic search of MEDLINE, EMBASE, the Cochrane Library (CENTRAL), and Web of Science identified relevant RCTs from start of recording to 2019. ELIGIBILITY CRITERIA: RCTs comparing opioids via intravenous PCA in acute pain, with comparable resulting pain scores and identical treatment with coanalgesics at study level. The quality of studies was assessed using the Cochrane risk of bias tool with six items. RESULTS: 52 RCTs were identified with data for 16 opioids. Primary endpoint was the inverted ratio of means of the total consumption administered via PCA, which resembles the analgesic potency. The calculated analgesic potencies were sufentanil 423 [95 percent CI 334.99; 532.96], fentanyl 58 [48.22; 68.60], buprenorphine 37 [26.66; 50.81], remifentanil 13 [9.37; 19.13], alfentanil 7 [4.02; 11.01], hydromorphone 6 [4.96; 8.43], oxymorphone 6 [4.46; 8.84], butorphanol 4.5 [3.05; 6.73], diamorphine 2.2 [1.16; 4.10], morphine 1, oxycodone 0.9 [0.65; 1.34], piritramide 0.9 [0.55; 1.56], nalbuphine 0.7 [0.54; 0.95], pethidine 0.12 [0.10; 0.15], meptazinol 0.08 [0.03; 0.20], and tramadol 0.08 [0.07; 0.10]. CONCLUSIONS: The results in part contradict the values from the literature, which have been criticized for their imprecision. From clinical experience however, our findings seem very plausible. Short-acting opioids are less potent compared to longer acting drugs, eg, morphine, probably due to shorter intervals for -readministration.