A Comparison of Differences Between the Systemic Pharmacokinetics of Levobupivacaine and Ropivacaine During Continuous Epidural Infusion: A Prospective, Randomized, Multicenter, Double-Blind Controlled Trial.

BACKGROUND: Epidural infusion of levobupivacaine and ropivacaine provides adequate postoperative pain management by minimizing side effects related to IV opioids and improving patient outcome. The safety profile of different drugs can be better estimated by comparing their pharmacokinetic profiles than by considering their objective side effects. Because levobupivacaine and ropivacaine have different pharmacokinetic properties, our aim was to investigate whether there is a difference in the pharmacokinetic variability of the 2 drugs in a homogeneous population undergoing continuous epidural infusion. This double-blind, multicenter, randomized, controlled trial study was designed to compare the pharmacokinetics of continuous thoracic epidural infusion of levobupivacaine 0.125% or ropivacaine 0.2% for postoperative pain management in adult patients who had undergone major abdominal, urological, or gynecological surgery. This study is focused on the evaluation of the coefficient of variation (CV) to assess the equivalence in the systemic exposure and interindividual variability between levobupivacaine and ropivacaine and, therefore, the possible differences in the predictability of the plasmatic concentrations of the 2 drugs during thoracic epidural infusion. METHODS: One hundred eighty-one adults undergoing major abdominal surgery were enrolled in the study. Patients were randomized to receive an epidural infusion of levobupivacaine 0.125% + sufentanil 0.75 µg/mL or of ropivacaine 0.2% + sufentanil 0.75 µg/mL at 5 mL/h for 48 hours. The primary end point of this study was to analyze the variability of plasma concentration of levobupivacaine and ropivacaine via an area under the curve within a range of 15% of the CV during 48 hours of continuous epidural infusion. The CV shows how the concentration values of local anesthetics are scattered around the median concentration value, thus indicating the extent to which plasma concentration is predictable during infusion. Secondary end points were to assess the pharmacologic profile of the local anesthetics used in the study, including an analysis of mean peak plasma concentrations, and also to assess plasma clearance, side effects, pain intensity (measured with a verbal numeric ranging score, i.e., static Numeric Rating Scale [NRS] and dynamic NRS]), and the need for rescue doses. RESULTS: The comparison between the 2 CVs showed no statistical difference: the difference between area under the curve was within the range of 15%. The CV was 0.54 for levobupivacaine and 0.51 for ropivacaine (P = 0.725). The plasma concentrations of ropivacaine approached the Cmax significantly faster than those of levobupivacaine. Clearance of ropivacaine decreases with increasing patient age. There were no significant differences in NRS, dynamic NRS scores, the number of rescue doses, or in side effects between groups. CONCLUSIONS: Considering the CV, the interindividual variability of plasma concentration for levobupivacaine and ropivacaine is equivalent after thoracic epidural infusion in adults. We found a reduction in clearance of ropivacaine depending on patient age, but this finding could be the result of some limitations of our study. The steady-state concentration was not reached during the 48-hour infusion and the behavior of plasma concentrations of ropivacaine and levobupivacaine during continuous infusions lasting more than 48 hours remains to be investigated, because they could reach toxic levels. Finally, no differences in the clinical efficacy or in the incidence of adverse effects between groups were found for either local anesthetic.

Postoperative Analgesia after Laparoscopic Ovarian Cyst Resection: Double-blind Multicenter Randomized Control Trial Comparing Intraperitoneal Nebulization and Peritoneal Instillation of Ropivacaine.

STUDY OBJECTIVE: To compare the effects of local anesthetic intraperitoneal nebulization with intraperitoneal instillation during laparoscopic ovarian cystectomy on postoperative morphine consumption and pain. DESIGN: Multicenter, randomized, case-control trial. DESIGN CLASSIFICATION: Canadian Task Force Classification I. SETTING: University hospitals in Italy. PATIENTS: One hundred forty patients scheduled for laparoscopic ovarian cystectomy. INTERVENTIONS: Patients were randomized to receive either nebulization of ropivacaine 150 mg before surgery or instillation of ropivacaine 150 mg before surgery. Nebulization was performed using the Aeroneb Pro device (Aerogen, Galway, Ireland). MEASUREMENTS AND MAIN RESULTS: One hundred forty patients were enrolled, and 123 completed the study. There was no difference between the 2 groups in average morphine consumption (7.3 ± 7.5 mg in the nebulization group vs 9.2 ± 7.2 mg in the instillation group; p = .17). Eighty-two percent of patients in the nebulization group required morphine compared with 96% in the instillation group (p < .05). Patients receiving nebulization had a lower dynamic Numeric Ranking Scale compared with those in the instillation group in the postanesthesia care unit postanesthesia care unit and 4 hours after surgery (p < .05). Ten patients (15%) in the nebulization group experienced shivering in the postanesthesia care unit compared with 2 patients (4%) in the instillation group (p = .035). CONCLUSION: Nebulization of ropivacaine prevents the use of morphine in a significant proportion of patients, reduced postoperative pain during the first hours after surgery, and was associated with a higher incidence of postoperative shivering when compared with instillation.

Emergence delirium, pain or both? A challenge for clinicians.

BACKGROUND: Children commonly display early postoperative negative behavior (e-PONB) after general anesthesia, which includes emergence delirium (ED), discomfort, temperament, and pain. However, it is often difficult for the caregiver to discriminate between various aspects of e-PONB. OBJECTIVE: This prospective observational study evaluates the possibility to distinguish between ED and pain in young children using validated pediatric observational scales in the early postoperative phase. METHODS: Following institutional approval and written consent, children undergoing elective adenoidectomy and/or tonsillectomy were enrolled. Following standardized anesthesia, two trained observers simultaneously evaluated children's behavior with the Paediatric Anaesthesia Emergence Delirium Scale (PAED) and with the Face, Legs, Activity, Cry, Consolability scale (FLACC) at extubation, and at 5, 10, and 15 min. RESULTS: Of 150 children that completed the study, 32 (21%) had ED, 7 (5%) had pain, and 98 (65%) had simultaneously both ED and pain. The association of 'No eye contact', 'No purposeful action' and 'No awareness of surroundings' (ED1) had a sensitivity of 0.96 and a specificity of 0.80 (PPV 0.97, NPV 0.78) to identify ED. 'Inconsolability' and 'Restlessness' (ED2) had a sensitivity of 0.69 and a specificity of 0.88 (PPV 0.83 and NPV 0.78) to identify pain. CONCLUSION: It is difficult to differentiate between ED and pain using FLACC and PAED scores. 'No eye contact', 'No purposeful action', and 'No awareness of surroundings' significantly correlated with ED. 'Inconsolability' and 'Restlessness' are not reliable enough to identify pain or ED in the first 15 min after awakening.

Effects of peritoneal ropivacaine nebulization for pain control after laparoscopic gynecologic surgery.

STUDY OBJECTIVE: To evaluate the effects of peritoneal cold nebulization of ropivacaine on pain control after gynecologic laparoscopy. DESIGN: Evidence obtained from a properly designed, randomized, double-blind, placebo-controlled trial (Canadian Task Force classification I). SETTING: Tertiary care center. PATIENTS: One hundred thirty-five women with American Society of Anesthesiologists disease classified as ASA I-III who were scheduled to undergo operative laparoscopy. INTERVENTION: Patients were randomized to receive either nebulization of 30 mg ropivacaine before surgery (preoperative group), nebulization of 30 mg ropivacaine after surgery (postoperative group), instillation of 100 mg ropivacaine before surgery (instillation group), or instillation of saline solution (control group). Nebulization was performed using the Aeroneb Pro device. MEASUREMENT AND MAIN RESULTS: Pain scores, morphine consumption, and ambulation time were collected in the post-anesthesia care unit and at 4, 6, and 24 hours postoperatively. One hundred eighteen patients completed the study. Patients in the preoperative group reported lower pain Numeric Ranking Scale values compared with those in the control group (net difference 2 points; 95% confidence interval [CI], 0.3-3.1 at 4 hours, 1-3 at 6 hours, and 0.7-3 at 24 hours; p = .01) Patients in the preoperative group consumed significantly less morphine than did those in the control group (net difference 7 mg; 95% CI, 0.7-13; p = .02). More patients who received nebulization walked without assistance within 12 hours after awakening than did those in the instillation and control groups (net difference 15%; 95% CI, 6%-24%; p = .001). CONCLUSIONS: Cold nebulization of ropivacaine before surgery reduced postoperative pain and morphine consumption and was associated with earlier walking without assistance.

The effect of fentanyl and clonidine on early postoperative negative behavior in children: a double-blind placebo controlled trial.

BACKGROUND: Early negative postoperative behavior (e-PONB) is common in children and manifests itself as emergence agitation (EA), emergence delirium (ED), and pain. The objective of this prospective double blind, randomized, placebo-controlled trial was to determine whether IV clonidine or IV fentanyl prior to surgery modifies e-PONB in children. METHODS: Ninety children scheduled for subumbilical surgery under sevoflurane anesthesia supplemented with regional anesthesia were randomized to either receive IV clonidine 2 mcg·kg(-1) , IV fentanyl 2 mcg·kg(-1) or placebo (IV saline) before surgery. Primary outcome measures were the incidence of EA, ED and pain during the first hour after awakening. Secondary outcome measures were side effects such as nausea and vomiting and delayed discharge from PACU. RESULTS: Eighty-seven children (n = 29 per group) completed the study. EA was present in 10 children (six clonidine, none fentanyl, and four placebo, P = 0.04) whereas ED was observed in 20 children (nine clonidine, three fentanyl, and eight placebo P = 0.13). Sixteen children who received placebo had a CHIPPS score of ≥4 compared with nine children in fentanyl group and 18 children receiving clonidine (P = 0.04). Ten children receiving fentanyl vomited during the first postoperative day, compared with six children in placebo group and none in clonidine group (P = 0.003). Discharge from PACU was not affected. CONCLUSIONS: IV fentanyl before surgery but not IV clonidine modifies e-PONB in children undergoing lower abdominal surgery under general anesthesia supplemented with regional anesthesia. The use of fentanyl in this population was also associated with reduced pain scores after awakening but with significantly greater incidence of PONV.

Incidence of pain after craniotomy in children.

BACKGROUND: There is very few information regarding pain after craniotomy in children. OBJECTIVES: This multicentre observational study assessed the incidence of pain after major craniotomy in children. METHODS: After IRB approval, 213 infants and children who were <10 years old and undergoing major craniotomy were consecutively enrolled in nine Italian hospitals. Pain intensity, analgesic therapy, and adverse effects were evaluated on the first 2 days after surgery. Moderate to severe pain was defined as a median FLACC or NRS score ≥ 4 points. Severe pain was defined as a median FLACC or NRS score ≥ 7 points. RESULTS: Data of 206 children were included in the analysis. The overall postoperative median FLACC/NRS scores were 1 (IQR 0 to 2). Twenty-one children (16%) presented moderate to severe pain in the recovery room and 14 (6%) during the first and second day after surgery. Twenty-six children (19%) had severe pain in the recovery room and 4 (2%) during the first and second day after surgery. Rectal codeine was the most common weak opiod used. Remifentanil and morphine were the strong opioids widely used in PICU and in general wards, respectively. Longer procedures were associated with moderate to severe pain (OR 1.30; CI 1.07-1.57) or severe pain (OR 1.41; 1.09-1.84; P < 0.05). There were no significant associations between complications, pain intensity, and analgesic therapy. CONCLUSION: Children receiving multimodal analgesia experience little or no pain after major craniotomy. Longer surgical procedures correlate with an increased risk of having postoperative pain.

The effects of propofol and ketamine on the cytokine levels of children with acute lymphoblastic leukemia.

The immune system of children with acute lymphoblastic leukemia (ALL) is affected by both the underlying disease and the chemotherapy. Children with ALL receive sedation for diagnostic and therapeutic procedures, which may contribute to immune competence alteration. The effects of propofol-ketamine combination on the immune system of children with ALL have not been investigated. This cohort study was designed to assess the immunomodulatory activity of the propofol-ketamine combination on proinflammatory and anti-inflammatory cytokines of children with ALL undergoing painful procedures. We enrolled 20 children with ALL undergoing bone marrow aspiration (BMA) and lumbar puncture with methotrexate. All children received sedation with IV ketamine (0.5 mg/kg) and propofol (3±2 mg/kg). Plasma concentration of cytokines interleukin (IL)-1ß, IL-2, IL-6, IL-10, IL-8, IL-12p70, and interferon-γ before sedation for BMA was represented as T0, during lumbar puncture with methotrexate sedation 6 hours after T0 was represented as T1, and 24 hours after BMA was represented as T2. Sedation with propofol-ketamine combination did not modify the plasma concentration of the most measured cytokines and the T helper 1/2 ratio in children with ALL. There was a significant reduction in IL-8 concentration 24 hours after BMA associated with the concomitant administration of steroids and methotrexate. These data suggest that sedation with propofol-ketamine combination may not affect the immediate outcome of children with ALL.

Emergence from General Anaesthesia: Can We Discriminate between Emergence Delirium and Postoperative Pain?

Unsettled behaviors characterize the early phase after general anaesthesia in the pediatric population in up to 80% of cases. Emergence delirium (ED) and acute pain are the two most relevant sources of this phenomenon. Research and clinical guidelines are difficult to implement due to the variability of the definition of unsettled behavior and measurement of the different components. The most probable incidence of ED is between 10% and 20%, and the potential risk factors could be summarized as young age, male gender, preoperative anxiety, baseline sleep-disordered breathing, volatile anaesthesia and ENT or ophthalmologic surgery. Self-reporting behavioral and observational scales are unable to reliably differentiate between ED and pain in a child who is not fully awake, making correct treatment choices difficult. This may lead to an undertreatment of pain in agitated children or to the overuse of opioids for self-limiting ED. This paper considers the current knowledge on the identification and treatment of ED and pain and provides a pragmatic approach for daily practice.

Association between the Use of Quantitative Sensory Testing and Conditioned Pain Modulation and the Prescription of Medication and Interventional Procedures in Children with Chronic Pain Conditions.

The evidence supporting the use of pharmacological treatments in pediatric chronic pain is limited. Quantitative sensory testing (QST) and conditioned pain modulation evaluation (CPM) provide information on pain phenotype, which may help clinicians to tailor the treatment. This retrospective study aimed to evaluate the association between the use of QST/CPM phenotyping on the selection of the treatment for children with chronic pain conditions. We retrospectively analyzed the medical records of 208 female patients (mean age 15 ± 2 years) enrolled in an outpatient interdisciplinary pediatric complex pain center. Pain phenotype information (QST/CPM) of 106 patients was available to the prescribing physician. The records of 102 age- and sex-matched patients without QST/CPM were used as controls. The primary endpoint was the proportion of medications and interventions prescribed. The secondary endpoint was the duration of treatment. The QST/CPM group received less opioids (7% vs. 28%, respectively, p < 0.001), less anticonvulsants (6% vs. 25%, p < 0.001), and less interventional treatments (29% vs. 44%, p = 0.03) than controls. Patients with an optimal CPM result tended to be prescribed fewer antidepressants (2% vs. 18%, p = 0.01), and patients with signs of allodynia and/or temporal summation tended to be prescribed fewer NSAIDs (57% vs. 78%, p = 0.04). There was no difference in the duration of the treatments between the groups. QST/CPM testing appears to provide more targeted therapeutic options resulting in the overall drop in polypharmacy and reduced use of interventional treatments while remaining at least as effective as the standard of care.

Moral Distress in Healthcare Providers Who Take Care of Critical Pediatric Patients throughout Italy-Cultural Adaptation and Validation of the Italian Pediatric Instrument.

BACKGROUND: Although Moral Distress (MD) is a matter of concern within the Pediatric Intensive Care Unit (PICU), there is no validated Italian instrument for measuring the phenomenon in nurses and physicians who care for pediatric patients in Intensive Care. The authors of the Italian Moral Distress Scale-Revised (Italian MDS-R), validated for the adult setting, in 2017, invited further research to evaluate the generalizability of the scale to clinicians working in other fields. Our study aims to reduce this knowledge gap by developing and validating the pediatric version of the Italian MDS-R. METHODS: We evaluated the new instrument for construct validity, then we administered it in a multicenter, web-based survey that involved healthcare providers of three PICUs and three adult ICUs admitting children in northern, central, and southern Italy. Finally, we tested it for internal consistency, confirmatory factorial validity, convergent validity, and differences between groups analysis. RESULTS: The 14-item, three-factor model best fit the data. The scale showed good reliability (a = 0.87). Still, it did not correlate with the Emotional Exhaustion and Depersonalization sub-scales of the Maslach Burnout Inventory (MBI) or with the 2-item Connor-Davidson Resilience Scale (CD-RISC 2) or the Satisfaction with Life Scale (SWLS). A mild correlation was found between the Italian Pediatric MDS-R score and intention to resign from the job. No correlation was found between MD and years of experience. Females, nurses, and clinicians who cared for COVID-19 patients had a higher MD score. CONCLUSIONS: The Italian Pediatric MDS-R is a valid and reliable instrument for measuring MD among Italian health workers who care for critically ill children. Further research would be helpful in better investigating its applicability to the heterogeneous scenario of Italian Pediatric Critical Care Medicine.

Intraperitoneal ropivacaine nebulization for pain management after laparoscopic cholecystectomy: a comparison with intraperitoneal instillation.

BACKGROUND: Studies evaluating intraperitoneal local anesthetic instillation for pain relief after laparoscopic procedures have reported conflicting results. In this randomized, double-blind study we assessed the effects of intraperitoneal local anesthetic nebulization on pain relief after laparoscopic cholecystectomy. METHODS: Patients undergoing elective laparoscopic cholecystectomy were randomly assigned to receive either instillation of ropivacaine 0.5%, 20 mL after induction of the pneumoperitoneum, or nebulization of ropivacaine 1%, 3 mL before and after surgery. Anesthetic and surgical techniques were standardized. Degree of pain at rest and on deep breathing, incidence of shoulder pain, morphine consumption, unassisted walking time, and postoperative nausea and vomiting were evaluated at 6, 24, and 48 hours after surgery. RESULTS: Of the 60 patients included, 3 exclusions occurred for conversion to open surgery. There were no differences between groups in pain scores or in morphine consumption. No patients in the nebulization group presented significant shoulder pain in comparison with 83% of patients in the instillation group (absolute risk reduction -83, 95% CI -97 to -70, P<0.001). Nineteen (70%) patients receiving nebulization walked without assistance within 12 hours after surgery in comparison with 14 (47%) patients receiving instillation (absolute risk reduction -24, 95% CI -48 to 1, P=0.04). One (3%) patient in the instillation group vomited in comparison with 6 (22%) patients in the nebulization group (absolute risk reduction -19%, 95% CI -36 to -2, P=0.03). CONCLUSIONS: Intraperitoneal ropivacaine nebulization was associated with reduced shoulder pain and unassisted walking time but with an increased incidence of postoperative vomiting after laparoscopic cholecystectomy.

Transnasal Sphenopalatine Ganglion Block for the Preventive Treatment of Chronic Daily Headache in Adolescents.

Chronic headaches are a major source of morbidity in the pediatric population, affecting physical function, school attendance, social capacity, mood, and sleep. In adults, repetitive sphenopalatine ganglion (SPG) blockade has been studied as a preventive treatment for chronic migraines. This case series aims to evaluate the SPG block for the preventive treatment of chronic daily headache (CDH) in adolescents. We prospectively evaluated 17 adolescents (14 females, 14 ± 1 year) with CDH not responding to cognitive behavioral therapy (CBT), physiotherapy, and standard medications. Each patient received 10 SPG blocks (two blocks/week) using the Tx360® device. At the end of treatment, 10 patients (59%) reported a Patient's Global Impression of Change (PGIC) score ≥ 67%, and 3 months after the end of treatment, nine patients (53%) sustained a PGIC ≥ 67%. There was also a statistically significant reduction in the depression subscale of the Revised Children's Anxiety and Depression Scale (RCADS) at the end of treatment and 3 months post-treatment compared with baseline. The procedure was well tolerated with no adverse effects. In our study, the use of repeat SPG blockade was associated with sustained benefits on the PGIC and the depression subscale of the RCADS when used as preventive headache treatment in adolescents with refractory CDH.

Xenon anaesthesia produces better early postoperative cognitive recovery than sevoflurane anaesthesia.

BACKGROUND AND OBJECTIVE: Xenon anaesthesia may have the potential to reduce postoperative cognitive impairment after general anaesthesia. This randomized double-blind controlled trial was designed to compare the early postoperative cognitive recovery after xenon and sevoflurane anaesthesia. METHODS: After institutional ethics approval, we obtained informed written consent from 60 adults, with American Society of Anesthesiologists I or II status, scheduled for elective surgery with an estimated surgery time between 60 and 360 min. Patients were randomized to receive xenon or sevoflurane anaesthesia. Both groups received a remifentanil infusion adjusted to clinical needs based on patients' haemodynamic and state entropy of less than 60. In cases of state entropy of at least 60 during the first 15 min after induction, patients in the xenon group received a propofol infusion targeted to state entropy of less than 60. The primary end-point of the study was the early postoperative cognitive recovery evaluated by the Short Orientation Memory Concentration Test. RESULTS: There was no significant difference in the mean preoperative Short Orientation Memory Concentration Test values between groups (sevoflurane 2.7 +/- 3.2 and xenon 3.2 +/- 2.6; P, 0.53). Awakening was significantly faster in the xenon group (sevoflurane 8 +/- 4 min and xenon 3 +/- 1 min; P < 0.001). Patients receiving xenon presented significantly lower Short Orientation Memory Concentration Test scores at 30 min (sevoflurane 6.7 +/- 5.9 and xenon 3.3 +/- 3.1; P 0.003) and 60 min (xenon 2.1 +/- 3 and sevoflurane 5 +/- 4.1; P 0.003) after extubation. CONCLUSION: Xenon anaesthesia was associated with faster emergence and with better early postoperative cognitive recovery than sevoflurane anaesthesia.

Peritoneal Nebulization of Ropivacaine during Laparoscopic Cholecystectomy: Dose Finding and Pharmacokinetic Study.

Background. Intraperitoneal nebulization of ropivacaine reduces postoperative pain and morphine consumption after laparoscopic surgery. The aim of this multicenter double-blind randomized controlled trial was to assess the efficacy of different doses and dose-related absorption of ropivacaine when nebulized in the peritoneal cavity during laparoscopic cholecystectomy. Methods. Patients were randomized to receive 50, 100, or 150 mg of ropivacaine 1% by peritoneal nebulization through a nebulizer. Morphine consumption, pain intensity in the abdomen, wound and shoulder, time to unassisted ambulation, discharge time, and adverse effects were collected during the first 48 hours after surgery. The pharmacokinetics of ropivacaine was evaluated using high performance liquid chromatography. Results. Nebulization of 50 mg of ropivacaine had the same effect of 100 or 150 mg in terms of postoperative morphine consumption, shoulder pain, postoperative nausea and vomiting, activity resumption, and hospital discharge timing (>0.05). Plasma concentrations did not reach toxic levels in any patient, and no significant differences were observed between groups (P > 0.05). Conclusions. There is no enhancement in analgesic efficacy with higher doses of nebulized ropivacaine during laparoscopic cholecystectomy. When administered with a microvibration-based aerosol humidification system, the pharmacokinetics of ropivacaine is constant and maintains an adequate safety profile for each dosage tested.

Human Genetic Variability Contributes to Postoperative Morphine Consumption.

UNLABELLED: High interindividual variability in postoperative opioid consumption is related to genetic and environmental factors. We tested the association between morphine consumption, postoperative pain, and single nucleotide polymorphisms (SNPs) within opioid receptor µ 1 (OPRM1), catechol-O-methyltransferase (COMT), uridine diphosphate glucose-glucuronosyltransferase-2B7, and estrogen receptor (ESR1) gene loci to elucidate genetic prediction of opioid consumption. We analyzed 20 SNPs in 201 unrelated Caucasian patients who underwent abdominal surgery and who were receiving postoperative patient-controlled analgesia-administered morphine. Morphine consumption and pain intensity were dependent variables; age and sex were covariates. A haplotype of 7 SNPs in OPRM1 showed significant additive effects on opioid consumption (P = .007); a linear regression model including age and 9 SNPs in ESR1, OPRM1, and COMT explained the highest proportion of variance of morphine consumption (10.7%; P = .001). The minimal model including 3 SNPs in ESR1, OPRM1, and COMT explained 5% of variance (P = .007). We found a significant interaction between rs4680 in COMT and rs4986936 in ESR1 (P = .007) on opioid consumption. SNPs rs677830 and rs540825 of OPRM1 and rs9340799 of ESR1 were nominally associated with pain Numeric Rating Scale scores. Combinations of genetic variants within OPRM1, COMT, and ESR1 better explain variability in morphine consumption than single genetic variants. Our results contribute to the development of genetic markers and statistical models for future diagnostic tools for opioid consumption/efficacy. PERSPECTIVE: This article presents the efforts dedicated to detect correlations between the genetic polymorphisms and the clinical morphine effect self-administered by patients using a patient-controlled analgesia pump after major surgery. The clinical effect is expressed in terms of morphine consumption and pain scores. REGISTERED ON CLINICALTRIALS.GOV: NCT01233752.