Gastrointestinal Motility Disorders Correlate with Intracranial Bleeding, Opioid Use, and Brainstem Edema in Neurosurgical Patients.

BACKGROUND: Gastrointestinal (GI) motility disorders may be directly associated with the intensity of acute brain injury, edema of the brainstem, and opioid use in neurosurgical patients. METHODS: In this retrospective study, patient demographic characteristics, computed tomography (CT) scans, the occurrence of gastroparesis, constipation, and opioid use were registered during the intensive care unit (ICU) stay and correlated with days of mechanical ventilation, length of ICU stay, and survival. Gastroparesis was defined as residual gastric volume > 250 mL per day, and constipation was defined as the absence of stool for 3 days or more during the ICU stay. RESULTS: Of 207 neurosurgical patients screened, 69 adult patients who spent more than 4 days in the ICU were included in the study. Gastroparesis was observed in 48 (69.6%) patients, constipation was observed in 67 (97.1%) patients, and stress ulcers were observed in 4 (5.8%) patients. Patients with brainstem edema (n = 57, 82.6%) had the first stool evacuation later compared with patients with no edema (8 [interquartile range (IQR) 5.25-9.75] vs. 3.5 [IQR 2.25-4] days; P < 0.001). In the logistic regression analysis, factors that were associated with GI dysmotility were central nervous system (CNS) bleeding (odds ratio [OR] 5.1, 95% confidence interval [CI] 1.26-20.8, P = 0.02), opioid use > 19.3 morphine equivalents (ME) per day (OR 5.37, 95% CI 1.1-27.1, P = 0.04), and brainstem edema (OR 4.9, 95% CI 1.1-21.6, P = 0.04). A receiver operating characteristic curve analysis confirmed that the cutoff value of > 6.78 ME per day was a good predictor determining GI dysmotility, with 89.5% sensitivity and 72.7% specificity (95% CI 0.67-0.88, area under the curve 0.784, Youden index 0.62, P = 0.001). Poor survival correlated with lower Glasgow Coma Score values (ρ = - 520, P < 0.001), CNS bleeding (ρ = 0.393, P < 0.001), associated cardiac diseases (ρ = 0.279, P < 0.001), and cardiorespiratory arrest on admission (ρ = 0.315, P < 0.001), but not with GI dysmotility (ρ = 0.175, P = 0.402). CONCLUSIONS: Significant correlation was registered between brainstem edema, gastrointestinal dysmotility, and opioids. CNS bleeding was the most important single factor influencing GI dysmotility. Further studies with opioid and nonopioid sedation may distinguish the influence of acute brain lesions versus drugs on GI dysmotility.

CHARACTERISTICS AND TREATMENT OUTCOMES OF UROLOGIC PATIENTS ADMITTED TO THE INTENSIVE CARE UNIT, OSIJEK UNIVERSITY HOSPITAL CENTER.

The postoperative care unit at the Department of Urology has significantly improved treatment of patients undergoing surgical procedures and reduced admission of urologic patients to the Intensive Care Unit (ICU). We examined the characteristics of urologic patients, time on mechanical ventilation, most common complications, and mortality in the period from January 2017 to March 2022. A total of 84 admissions to ICU were recorded, accounting for 1.5% of all patients having undergone surgical, therapeutic or diagnostic interventions under general or regional anesthesia at the Department of Urology. The most common reasons for admission to ICU were respiratory failure (79 patients), hemodynamic instability, and bleeding. The median time on mechanical ventilation was 9.7 [2.4-58.2] hours in urology patients vs. 6 [3-14.7] hours in the rest of surgical ICU patients (p=0.058). Hypertension and renal failure were more common in urologic than in the rest of surgical ICU patients (p<0.05). The overall mortality of urologic patients was lower than in the rest of surgical ICU patients (10.7% vs. 18.99%, p=0.08) but the difference did not reach statistical significance. Independently of the lower mortality, improvements in the outcome of urologic patients admitted to the ICU are feasible. Early identification of patients at risk of infections, postoperative respiratory failure, cardiovascular incidents, and bleeding may further reduce mortality and improve outcomes.

TRACHEOBRONCHIAL MORPHOMETRY CORRELATES WITH DEMOGRAPHIC CHARACTERISTICS AND INFECTIONS IN CRITICALLY ILL PATIENTS.

Tracheal measurements in the intensive care unit (ICU) are important for the choice of endotracheal tube and may correlate with patient demographic characteristics and infections. The study included 42 surgical patients, age 60 [48-71] years, who underwent diagnostic chest computed tomography (CT) scans during treatment in the ICU, Osijek University Hospital, in 2019 and 2020. CT scans were analyzed using AW Server 3.2. Measurement analysis showed that the diameters of the tracheobronchial tree, the length of the trachea and left main bronchus were significantly larger in men compared to women (p<0.05 all). The smallest tracheal upper diameter was 15.25 [IQR 11.8-18.8] mm vs. 17.95 [13.55-20.05] mm in septic and nonseptic patients, respectively (p=0.028). A total of 26 patients who underwent CT scans developed nosocomial pneumonia. It was right-sided in 15, left-sided in 6 and bilateral in 5 patients, and correlated significantly with the left main bronchus length (ρ=0.515, p=0.007). No correlation was observed between tracheobronchial measurements and length of ICU treatment, number of hours spent on mechanical ventilation, or survival. A larger study could provide better data on the importance of tracheobronchial tree measurements in ICU patients.

POINT-OF-CARE DIAGNOSTIC APPROACH IN A CRITICALLY ILL PATIENT WITH SEVERE BLEEDING FROM URINARY TRACT.

Coagulation disorders in critically ill patients presenting with bleeding can be multicausal. The drugs applied can interfere and impair the coagulation cascade. Point-of-care (POC) coagulation assays may resolve difficult therapeutic situations in critical illness. We report on a 73-year-old critically ill male patient with massive hematuria after bladder lithotripsy. The patient was on low molecular weight heparin therapy due to recent pulmonary embolism. He was subjected to repeated surgical hemostasis which was ineffective despite massive transfusion protocol and normal standard coagulation profile. Additional POC coagulation assays were obtained and were indicative of platelet dysfunction. We revised his medical therapy and suspected the possible drug influence on platelet aggregation. After discontinuation of target drug, platelet aggregation increased whereas hematuria stopped. Coagulation disorders in intensive care unit patients are often multifactorial. Standard laboratory tests are unreliable in complex refractory bleeding and may result in inappropriate therapeutic decisions. Stepwise approach with assessment of clinical parameters, present therapy, and a combination of POC coagulation tests is the key to optimal therapeutic management.

COMPARISON OF TRACHEAL ASPIRATES IN THE PERIOD BEFORE AND AFTER THE START OF THE COVID-19 PANDEMIC IN THE INTENSIVE CARE UNIT IN A TERTIARY HOSPITAL.

Changes in working methods and diagnostics using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) diagnostics that occurred after the start of the COVID-19 pandemic could show differences in the prevalence of positive microbiological samples. In a retrospective study, a total of 442 tracheal aspirates in the pre-pandemic period (Period A, 2018, 198 patients, age median 69 (57-78)) and 277 samples in the pandemic period (Period B, 2021, 147 patients, age 68 (56-77) (p=0.585) obtained after the start of the pandemic were analyzed. A total of 176 patients had at least 1 positive result. In Period A, there were 245 (55%) and in Period B 186 (68%) sterile samples (p=0.001). The most frequently isolated pathogens were Acinetobacter baumannii in 86 patients from Period A and 32 patients from Period B, i.e., 43% vs. 21.7% of all positive isolates (p=0.247), followed by Pseudomonas aeruginosa in 29 patients in Period A (14.6%) vs. 7 (3%) (p=0.112) in Period B. A statistically significant increase was observed in the incidence of Enterobacterales (16.6% vs. 32.6%, p=0.002), especially Klebsiellae spp. Although overall mortality decreased in Period B, changes in the working methods and diagnostics did not result in changes in the mortality of patients whose tracheal aspirates were sampled.

Bispectral Index Monitoring and Observer Rating Scale Correlate with Dreaming during Propofol Anesthesia for Gastrointestinal Endoscopies.

Background and objectives: Dreaming is a commonly reported side effect of propofol anesthesia. Materials and Methods: We investigated the inci-dence and character of dreams in patients undergoing intravenous propofol anesthesia and cor-related it with an observer rating scale of facial expression on the seven-point scale from pain to smile. A total of 124 patients undergoing gastrointestinal endoscopy were recruited in the pro-spective observational study. Bispectral index (BIS), blood pressure (BP), and pulse were moni-tored. Upon emergence from anesthesia, the patient's facial expression was rated numerically. Thereafter, patients were asked whether they had dreams and to rate their dreams as pleasant or unpleasant. The mean age of participants was 53; body mass index, 26.17; duration of procedure, 20 min; and average propofol dose, 265 mg. Results: Dreaming was reported by 43% of patients. Dreams were pleasant in all but one patient. There was a significant correlation of the observer's rating of facial expression with dreaming (r = 0.260; p = 0.004). Dreamers had higher scores of observer rating of facial expression (1 (0-2) vs. 0.5 (0-1), p = 0.006). Conclusions: BIS values were lower in the dreamers vs. non-dreamers 2 min after the endoscopy started (48 (43-62) vs. 59 (45-71), p = 0.038). Both BIS and observer ratings correlate with dreaming in patients undergoing gastrointestinal endos-copy. Trial registration number: NCT04235894.

ANALGESIC EFFECT OF TRAMADOL IS NOT ALTERED BY POSTOPERATIVE SYSTEMIC INFLAMMATION AFTER MAJOR ABDOMINAL SURGERY.

Tramadol is a commonly used analgesic in intensive care units (ICUs) for acute postoperative pain. Conversion of tramadol into active metabolites may be impaired in inflammatory states. Catechol-O-methyltransferase may influence pain. The aim of the study was to examine differences in the analgesic effect of tramadol between ICU patients with and without signs of systemic inflammation. Forty-three patients were admitted to ICU after a major abdominal surgery. The patients received a dose of 100 mg of tramadol intravenously every 6 hours during the first 24 hours after surgical procedure. Pain scores were measured by the Numeric Rating Scale before and 30 minutes after tramadol administration in awake patients. Systemic inflammation was considered when at least two of the following postoperative parameters were present in the first 24 hours of ICU admission: fever or hypothermia, tachycardia, pCO2 <4.3 kPa, white blood cells >12000/mm3 or <4000/mm3, or preoperative value of C-reactive protein (CRP) >50 mg/L or/and procalcitonin (PCT) >0.5 mg/L. Catechol-O-methyltransferase was analyzed postoperatively. Fifteen (34.8%) patients met the criteria for systemic inflammation. Tramadol was proven to be an effective analgesic for the treatment of postoperative pain regardless of the presence of systemic inflammation (p<0.05). Lower perception of pain before tramadol application was observed in patients with systemic inflammation, but the difference was not significant. A negative correlation was observed between the preoperative values of CRP and PCT and the analgesic effect of tramadol assessed at the second measurement point (r=-0.358, p=0.03, and r=-0.364, p=0.02, respectively). Catechol-O-methyltransferase variants were not in correlation with pain and opioid consumption. Based on our findings, tramadol is effective in lowering pain scores after major abdominal surgery irrespective of the presence of systemic inflammation.

DOES THE ANESTHESIA TECHNIQUE AFFECT ARTERIAL PRESSURE AND REGIONAL CEREBRAL OXYGEN SATURATION DURING SHOULDER ARTHROSCOPY IN THE BEACH CHAIR POSITION?

- This study aimed to investigate the impact of posture and anesthesia techniques on blood pressure changes, heart rate and regional cerebral oxygen saturation during shoulder arthroscopy in the beach chair position (BCP). Sixty patients were included in this prospective cohort study: 30 patients mechanically ventilated and subjected to general anesthesia (GA) and 30 patients subjected to interscalene block (ISB) without mechanical ventilation. Noninvasive blood pressure, heart rate (HR), peripheral blood oxygen saturation and regional oxygen saturation of the brain were measured in twelve predefined points during perioperative period. The GA group patients had significantly lower mean arterial pressure and heart rate values compared to patients in ISB group during BCP (p<0.001). There was a significant difference in regional cerebral saturation between the groups measured only in points of induction and emergence from anesthesia in favor of GA group when receiving 100% oxygen (p<0.001). Changes in the mean arterial pressure and regional cerebral oxygen saturation for both brain hemispheres correlated only at the 10th minute after setting up BCP in GA patients (right, p=0.004 and left, p=0.003). This correlation did not exist in the ISB group patients at any of the points measured. Cerebral desaturation events recorded in both groups were not statistically significantly different. Results of this study demonstrated that GA preserved regional cerebral oxygenation in a safe range during BCP despite changes in the arterial blood pressure and heart rate in comparison to ISB.

Ventilation Management in a Patient with Ventilation-Perfusion Mismatch in the Early Phase of Lung Injury and during the Recovery.

Chest trauma is one of the most serious and difficult injuries, with various complications that can lead to ventilation-perfusion (V/Q) mismatch and systemic hypoxia. We are presenting a case of a 53-year-old male with no chronic therapy who was admitted to the Intensive Care Unit due to severe respiratory failure after chest trauma. He developed a right-sided pneumothorax, and then a thoracic drain was placed. On admission, the patient was hemodynamically unstable and tachypneic. He was intubated and mechanically ventilated, febrile (38.9 °C) and unconscious. A lung CT showed massive non-ventilated areas, predominantly in the right lung, guiding repeated therapeutic and diagnostic bronchoalveolar lavages. He was ventilated with PEEP of 10 cmH2O with a FiO2 of 0.6-0.8. Empirical broad-spectrum antimicrobial therapy was immediately initiated. Both high FiO2 and moderate PEEP were maintained and adjusted according to the current blood gas values and oxygen saturation. He was weaned from mechanical ventilation, and non-invasive oxygenation was continued. After Stenotrophomonas maltophilia was identified and treated with sulfamethoxazole/trimethoprim, a regression of lung infiltrates was observed. In conclusion, both ventilatory and antibiotic therapy were needed to improve the oxygenation and outcome of the patient with S. maltophilia pneumonia and V/Q mismatch.

Advances in Analgosedation and Periprocedural Care for Gastrointestinal Endoscopy.

The number and complexity of endoscopic gastrointestinal diagnostic and therapeutic procedures is globally increasing. Procedural analgosedation during gastrointestinal endoscopic procedures has become the gold standard of gastrointestinal endoscopies. Patient satisfaction and safety are important for the quality of the technique. Currently there are no uniform sedation guidelines and protocols for specific gastrointestinal endoscopic procedures, and there are several challenges surrounding the choice of an appropriate analgosedation technique. These include categories of patients, choice of drug, appropriate monitoring, and medical staff providing the service. The ideal analgosedation technique should enable the satisfaction of the patient, their maximum safety and, at the same time, cost-effectiveness. Although propofol is the gold standard and the most used general anesthetic for endoscopies, its use is not without risks such as pain at the injection site, respiratory depression, and hypotension. New studies are looking for alternatives to propofol, and drugs like remimazolam and ciprofol are in the focus of researchers' interest. New monitoring techniques are also associated with them. The optimal technique of analgosedation should provide good analgesia and sedation, fast recovery, comfort for the endoscopist, patients' safety, and will have financial benefits. The future will show whether these new drugs have succeeded in these goals.

Predictive role of selected biomarkers in differentiating gram-positive from gram-negative sepsis in surgical patients: a retrospective study.

INTRODUCTION: Patients after major surgery are at high risk of developing sepsis, which is accompanied by elevated serum levels of C-reactive protein (CRP) and procalcitonin (PCT). This study aimed to examine the differences in serum biomarker levels concerning the causative agent of sepsis in surgical patients. MATERIAL AND METHODS: A retrospective study was carried out in the surgical intensive care unit (ICU) and included 81 septic patients admitted from January 2019 to May 2022, who had positive blood cultures (BC). Serum levels of PCT, CRP, white blood cells (WBC) and platelet counts were recorded on the day of the positive BC and over the following 3 days. RESULTS: Patients with gram(-) sepsis had significantly higher PCT levels, and lower platelet count compared to patients with gram(+) sepsis. High PCT and low platelets levels in all measurements were a significant predictor of gram(-) isolate with the highest predictive value on the third day after BC sampling, with AUROC 0.821 (95% CI: 0.692-0.950), P = 0.001, and AUROC 0.676 (95% CI: 0.541-0.811), P = 0.02, respectively. In multivariate logistic regression, platelets the day after BC sampling and PCT on the third day made a significant contribution in distinguishing gam(+) from gram(-) BC. Age and high serum CRP levels were significant predictors of poor outcomes. CONCLUSIONS: PCT and platelets may be useful biomarkers for predicting the causative agent of sepsis in surgical patients.

Corrigendum: Different pharmacokinetics of tramadol, O-demethyltramadol and N-demethyltramadol in postoperative surgical patients from those observed in medical patients.

[This corrects the article DOI: 10.3389/fphar.2021.656748.].

Long-Term Outcomes of Breast Cancer Patients Receiving Levobupivacaine Wound Infiltration or Diclofenac for Postoperative Pain Relief.

Breast cancer is the most common malignant disease in women. Preclinical studies have confirmed that the local anesthetic levobupivacaine has a cytotoxic effect on breast cancer cells. We examined whether postoperative wound infiltration with levobupivacaine influences survival in 120 patients who were operated on for breast cancer and underwent quadrantectomy or mastectomy with axillary lymph node dissection. Groups with continuous levobupivacaine wound infiltration, bolus wound infiltration, and diclofenac analgesia were compared. Long-term outcomes examined were quality of life, shoulder disability, and hand grip strength (HGS) after one year and survival after 5 and 10 years. Groups that had infiltration analgesia had better shoulder function compared to diclofenac after one year. The levobupivacaine PCA group had the best-preserved HGS after 1 year (P = 0.022). The most significant predictor of the 5-year outcome was HGS (P = 0.03). Survival at 10 years was 85%, 92%, and 77% in the diclofenac, levobupivacaine bolus, and levobupivacaine PCA groups (ns. P = 0.36). The extent of the disease at the time of surgery is the most important predictor of long-term survival (P = 0.03). A larger prospective clinical study could better confirm the effect of levobupivacaine wound infiltration on outcomes after breast cancer surgery observed in this pilot study-trial number NCT05829707.

[Placebo in the pain treatment]. / Placebo u lijecenju boli.

Use of medical preparations having no specific pharmacological activity or dummy procedures administered to patients is known as placebo. Such maneuvers are important in the pain treatment and clinical studies investigating pain mechanisms. Several recent studies have shown that placebo treatment produces measurable psychophysiological effects, characterized by changes in specific brain functions and decreased subjective pain perception. This article reviews changes observed in placebo analgesia, its intensity as compared to active compounds, and principal problems observed during the placebo treatment and in clinical trials.

Management of Anesthesia and Perioperative Procedures in a Child with Glucose-6-Phosphate Dehydrogenase Deficiency.

Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme that helps red blood cells work properly; it participates in the production of antioxidants and helps to defend cells against oxidative damage. With all this in mind, patients with G6PD deficiency may be very sensitive and vulnerable to different oxidative stressors, because they can cause some serious medical conditions of which hemolytic anemia is common in adults and severe jaundice in newborns. The most common triggers of hemolysis in G6PD deficiency are infections, medications, metabolic conditions such as diabetic ketoacidosis, hypothermia, and a very important item-surgical stress. During the operative period, the anesthetic goal is to reduce stress and monitor if the hemolysis occurs, and of course, treat it if it occurs. In our case, the combination of sevoflurane inhalation anesthesia with the addition of sufentanil proved to be safe and effective in the management of a child with G6PD deficiency.

Integrity of gut mucosa during anaesthesia in major abdominal surgery.

The aim of the study was to examine a perfusion and integrity of small bowel in 60 subsequent patients during the major open abdominal surgery which lasted from 2 to 7 hours. Two samples of the intestinal mucosa were removed: at the beginning, and at the end of the surgical procedure in general anaesthesia. A mucosal injury was classified into 4 grades. pH, PCO2 and lactate level were measured in the blood samples from the arterial and mesenteric vein in one hour time intervals. The changes of intestinal mucosa were found in 31 patients (51.7%): in 19 patients (31.7%) grade 1 changes were recorded, in 10 patients (16.7%) grade 2, and in 2 patients (3.3%) grade 3. Grade 4 lesions were not recorded. There was a statistically significant correlation between grades of the mucosal damage and the surgery duration (p = 0.001). Analysis during the one hour intervals showed that there was no exact time point when the significant aggravation of the pathohistological changes in intestinal mucosa occurred. However, when patients were allocated into two subgroups with surgical procedures lasting less than 4 hours and more than 4 hours, there was a statistically significant difference in the grades of mucosal damage between subgroups (p < 0.05). More biopsies without pathohistological changes were observed in the patients whose procedure duration was < 4 hours. A significantly higher lactate concentrations in arterial and mesenteric venous blood were observed in the patients with pathohistological changes at 6 hours time point as compared to 2 hour time point in the patients without pathohistological changes (p < 0.05). During the open abdominal surgery in general anaesthesia, the length of the procedure influences the grade of the intestinal mucosa injury. Deterioration of the pathohistological findings in the intestinal mucosa correlates with high lactate blood level, suggesting that the cause of these changes may result from tissue hypoxia.

[Sugammadex, a new drug for reversion of muscle relaxants]. / Sugamadeks, novi antagonist misicnih relaksatora.

Sugammadex is a new pharmacological agent for neuromuscular block reversion. It is a cyclic oligosaccharide, a gamma cyclodextrin with lipophylic inner coat that enables forming of stable complexes with steroidal neuromuscular blocking drugs, especially with rocuronium. A physical encapsulation of the relaxants is a novel elimination pathway and it produces fast and complete reversion of both deep and shallow neuromuscular block. Consequently, sugammadex has no unwanted cholinergic muscarinic effects observed with cholinesterase inhibitors such as bradycardia, hypersalivation, and increased gastrointestinal motility. Since the effects of sugammadex are dose dependent it can very rapidly reverse the effects of rocuronium. After the adjusted dose of sugammadex was given, the duration of action of rocuronium can be made as short as that of succinylcholine. This characteristic is especially important in the 'can't intubate, can't ventilate' situation and after surgical procedure was unexpectedly finished. Clinical studies involving more patients are needed to show the real risk-benefit profile and safety in the special patients' populations.

Workload changes during the COVID-19 pandemic and effects on the flow of cancer patients in the Maxillofacial Surgery Department.

Aim A SARS Coronavirus 2 (COVID-19) pandemic drastically changed the way the health system works. In Croatia, lockdown measures to curb virus spread lasted from March to May 2020, and all non-essential medical procedures and patients' visits have been cancelled. The study aimed to compare patients' flow and interventions in the surgical department before, during and after the lockdown period. Methods This cross-sectional study analysed the workload at the Maxillofacial and Oral Surgery Department (Department), Osijek University Hospital, during the COVID-19 pandemic (March-May 2020) and four subsequent months. The same period of 2019 was compared as a control. The data were subtracted from hospitals' electronic database. Results During COVID-19 lockdown from March to May 2020 the number of hospitalizations (306 vs. 138), surgical procedures (306 vs. 157), and scheduled outpatient visits (2009 vs. 804), dropped significantly as compared to 2019. The number of skin tumour removals was halved (from 155 in 2019 to 58 in 2019) (p<0.001), and the number of emergency patients was unchanged in the 3-month period. A significant decrease in outpatient visits and hospital admissions continued after the lockdown (p<0.001). Conclusion A decrease in the number of outpatient visits, hospitalizations, and tumour removals may result in larger proportions of patients with advanced cancers in the future. The second wave of COVID-19 pandemic is ongoing, and special effort must be paid to reduce the number of cancer patients receiving suboptimal treatment.

Analgesia in the Neurosurgical Intensive Care Unit.

Acute pain in neurosurgical patients is an important issue. Opioids are the most used for pain treatment in the neurosurgical ICU. Potential side effects of opioid use such as oversedation, respiratory depression, hypercapnia, worsening intracranial pressure, nausea, and vomiting may be problems and could interfere with neurologic assessment. Consequently, reducing opioids and use of non-opioid analgesics and adjuvants (N-methyl-D-aspartate antagonists, α2 -adrenergic agonists, anticonvulsants, corticosteroids), as well as non-pharmacological therapies were introduced as a part of a multimodal regimen. Local and regional anesthesia is effective in opioid reduction during the early postoperative period. Among non-opioid agents, acetaminophen and non-steroidal anti-inflammatory drugs are used frequently. Adverse events associated with opioid use in neurosurgical patients are discussed. Larger controlled studies are needed to find optimal pain management tailored to neurologically impaired neurosurgical patients.

Different Pharmacokinetics of Tramadol, O-Demethyltramadol and N-Demethyltramadol in Postoperative Surgical Patients From Those Observed in Medical Patients.

Background: Most studies examining tramadol metabolism have been carried out in non-surgical patients and with oral tramadol. The aim of this study was 1) to measure concentrations of tramadol, O-demethyltramadol (ODT), and N-demethyltramadol (NDT) in the surgical patients admitted to the intensive care unit (ICU) within the first 24 postoperative hours after intravenous application of tramadol, and 2) to examine the effect of systemic inflammation on tramadol metabolism and postoperative pain. Methods: A prospective observational study was carried out in the surgical ICU in the tertiary hospital. In the group of 47 subsequent patients undergoing major abdominal surgery, pre-operative blood samples were taken for CYP2D6 polymorphism analysis. Systemic inflammation was assessed based on laboratory and clinical indicators. All patients received 100 mg of tramadol intravenously every 6 h during the first postoperative day. Postoperative pain was assessed before and 30 min after tramadol injections. Tramadol, ODT, and NDT concentrations were determined by high-performance liquid chromatography. Results: CYP2D6 analysis revealed 2 poor (PM), 22 intermediate (IM), 22 extensive (EM), and 1 ultrafast metabolizer. After a dose of 100 mg of tramadol, t1/2 of 4.8 (3.2-7.6) h was observed. There were no differences in tramadol concentration among metabolic phenotypes. The area under the concentration-time curve at the first dose interval (AUC1-6) of tramadol was 1,200 (917.9-1944.4) µg ×h ×L-1. NDT concentrations in UM were below the limit of quantification until the second dose of tramadol was administrated, while PM had higher NDT concentrations compared to EM and IM. ODT concentrations were higher in EM, compared to IM and PM. ODT AUC1-6 was 229.6 (137.7-326.2) µg ×h ×L-1 and 95.5 (49.1-204.3) µg ×h ×L-1 in EM and IM, respectively (p = 0.004). Preoperative cholinesterase activity (ChE) of ≤4244 U L-1 was a cut-off value for a prediction of systemic inflammation in an early postoperative period. NDT AUC1-6 were significantly higher in patients with low ChE compared with normal ChE patients (p = 0.006). Pain measurements have confirmed that sufficient pain control was achieved in all patients after the second tramadol dose, except in the PM. Conclusions: CYP2D6 polymorphism is a major factor in O-demethylation, while systemic inflammation accompanied by low ChE has an important role in the N-demethylation of tramadol in postoperative patients. Concentrations of tramadol, ODT, and NDT are lower in surgical patients than previously reported in non-surgical patients. Clinical Trial Registration: ClinicalTrials.gov, NCT04004481.