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.].

Effects of an intravenous lidocaine bolus before tracheal extubation on recovery after breast surgery - Lidocaine at the End (LATE) study: a randomized controlled clinical trial.

AIM: To investigate whether IV lidocaine improves emergence, early recovery, and late recovery after general anesthesia in women who undergo breast surgery. METHODS: Sixty-seven women with American Society of Anesthesiologists physical status I-II, scheduled for breast surgery were randomized to receive an IV lidocaine 1.5 mg/kg bolus (n=34) or saline placebo (n=33) before tracheal extubation. Anesthesia was induced with thiopental, vecuronium, and fentanyl, and maintained with sevoflurane~1 MAC and 50% nitrous-oxide in oxygen. No postoperative nausea and vomiting (PONV) prophylaxis was given. Time to extubation, bucking before extubation, and quality of emergence, as well as early and late recovery (coughing post-extubation, sore throat, PONV, and pain scores) within 24 hours postoperatively were evaluated. Diclofenac and meperidine were used for the treatment of pain and metoclopramide for PONV. RESULTS: The groups did not significantly differ in demographics, intraoperative data, or PONV risk scores. Extubation was~8 minutes in both groups. Patients who received IV lidocaine had significantly smoother recovery, both statistically and clinically; they had better extubation quality scores (1.5 [1-3] vs 3 [1-5], P<0.001), less bucking before extubation (38% vs 91%, P<0.001), less coughing after extubation (at 1 min 18% vs 42%, P=0.026; and at 24 hours 9% vs 27%, P=0.049), and less sore throat (6% vs 48%, P<0.001). Late PONV decreased (3% vs 24%, P=0.013). There were no differences in pain scores and treatment. CONCLUSION: In women who underwent breast surgery, IV lidocaine bolus administered just before extubation attenuated bucking, cough and sore throat, and PONV for 24 hours after general anesthesia, without prolonging the emergence.

Evaluation of continuous aspiration of subglottic secretions in prevention of microaspiration during general anesthesia: a randomized controlled pilot study.

AIM: To assess the difference between endotracheal tubes (ETT) with continuous suction of subglottic secretions (CASS) and standard ETT in preventing secretions movement from the pharynx into the trachea, past the inflated cuff during general anesthesia. METHODS: This randomized, controlled trial enrolled 50 patients who underwent general anesthesia for elective abdominal surgery lasting longer than two hours. They received either ETT with CASS: Teleflex ISIS HVT (GISIS, n=17) or Mallinckrodt TaperGuard Evac (GEvac, n=17), or ETT without suction: Mallinckrodt Intermediate Hi-Lo (GStand, n=16). Methylene blue dye solution (10 mL) was delivered into the hypopharynx every 60 minutes. Subglottic secretions were continuously suctioned. Fiberoptic bronchoscopy was performed every 20 minutes and during tracheal extubation to evaluate the dye location. RESULTS: The groups did not differ in age, sex, body mass index, race, American Society of Anesthesiologists status, and surgery type. Dye migrated past the inflated cuff into the distal trachea in no patient with ETT with CASS and in 13% of patients with standard ETT. On tracheal extubation, dye migrated into the distal trachea more often in the GStand group (56%), compared with the GEvac (13%) and GISIS group (29%) (P=0.045). The GISIS group had 26±19 mL of secretions suctioned from above the inflated cuff, while the GEvac group had 13±10 mL (P=0.05). CONCLUSION: Compared with standard ETT, ETT with CASS efficiently removed secretions during general anesthesia, prevented secretions from migrating past the inflated cuff, and significantly reduced the amount of secretions that reached the distal airways on tracheal extubation.

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.

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.

AMBULATORY EYE SURGERY AND ANTITHROMBOTIC THERAPY - NEW APPROACHES.

One of the most common surgeries in elderly patients is eye surgery. An increasing number of patients undergoing ambulatory eye surgery are on antithrombotic therapy. These drugs may increase the risk of perioperative bleeding associated with ophthalmic needle blocks and/or eye surgery. Intraoperative bleeding and postoperative hemorrhagic complications may lead to the loss of vision or even eyes. On the other hand, stopping anticoagulants and antiplatelets before the surgery may increase the risk of thrombotic events with potentially life-threatening complications. The aim of this narrative review is to provide a systematic review of the published evidence for the perioperative antithrombotic management of patients undergoing different types of eye surgery in ambulatory settings. A comprehensive review of the English-language medical literature search utilizing PubMed, Ovid Medline® and Google Scholar from January 2015 to December 2018 was performed. The database searches included studies providing evidence relevant to ambulatory eye surgery and perioperative antiplatelet medications and anticoagulants. Updated recommendations will be given for continuation, discontinuation, and modification of antithrombotic agents in order to optimize the management of antithrombotic therapies in outpatients scheduled for eye surgery.

Comparison of recovery after sugammadex or neostigmine reversal of rocuronium in geriatric patients undergoing spine surgery: a randomized controlled trial.

AIM: To evaluate the effect of sugammadex compared with neostigmine on speed and quality of recovery after rocuronium neuromuscular blockade (NMB) in geriatric patients undergoing posterior lumbar spine surgery. METHODS: This randomized controlled study at a tertiary academic medical center involved 40 patients (age ≥65 years, ASA PS II/III) scheduled for elective surgery under general anesthesia. Patients were randomized to sugammadex or neostigmine for reversal of moderate NMB with rocuronium. The primary outcome was recovery time from NMB after surgery to a train-of-four (TOF) ratio ≥0.9 measured at the adductor pollicis (TOF-Watch® SX). Secondary outcomes included hemodynamic change after administration of reversal agent (heart rate, blood pressure, dysrhythmia), time to extubation, pain medication requirement, time to first ambulation, and length of postanesthesia care unit (PACU) and total hospital stay. RESULTS: Sugammadex (4±2.2 min) compared with neostigmine reversal (26.3±17.5 min) was on average 22 min faster (95% CI 14.1-30.5; P≤0.001) with less variability (range 2-11 min vs 5-72 min). The groups significantly differed in time for tracheal extubation, response to verbal commands (open eyes, squeeze hand, lift head), and operating room exit. However, they had similar PACU stay, time to first ambulation, total hospital stay, postoperative pain, and opioid use. Sugammadex had less hemodynamic variability than neostigmine. No patient developed treatment-emergent dysrhythmias. CONCLUSION: Sugammadex reversal significantly hastened NMB recovery compared with neostigmine reversal in geriatric patients. It significantly decreased operating room time but not PACU time or hospital stay.

Epidural analgesia for acute ischemic pain after intra-arterial zolpidem injection in opioid-addicted patient-A case report.

A patient taking opioid maintenance therapy unintentionally injected dissolved zolpidem pills into the femoral artery and suffered acute limb ischemia. High amounts of opioids with supplemental therapies were inefficient for intractable ischemic pain, suggesting the presence of opioid-induced hyperalgesia (OIH). Epidural analgesia efficiently relieved pain and symptoms of OIH.

LOCAL ANESTHETICS AND STEROIDS: CONTRAINDICATIONS AND COMPLICATIONS - CLINICAL UPDATE.

The objective of this clinical update, based on recently published literature, was to discuss incidence and characteristics of the most relevant clinical adverse effects associated with local anesthetic and steroid use in regional anesthesia and treatment of acute or chronic pain. A comprehensive review of the English-language medical literature search utilizing PubMed, Ovid Medline® and Google Scholar from 2015 to 2018 was performed. This narrative review provides anesthesia practitioners with updated evidences on complications and contraindications of local anesthetic and steroid use with emphasis on current points of view regarding prevention, early diagnosis and treatment of adverse events.

Nitrous oxide added at the end of isoflurane anesthesia hastens early recovery without increasing the risk for postoperative nausea and vomiting: a randomized clinical trial.

BACKGROUND: Nitrous oxide (N2O) has been reported to increase the risk of postoperative nausea and vomiting (PONV) in a dose-dependent manner. We investigated the effect of adding N2O at the end of isoflurane inhalational anesthesia on the recovery and incidence of PONV. Our hypothesis was that N2O would reduce the time to early recovery without increasing the incidence of PONV. METHODS: After obtaining ethics committee approval and written informed consent, 100 women at American Society of Anesthesiologists physical status I-III and scheduled for laparoscopic-assisted vaginal hysterectomy were randomized into two groups (G) according to the carrier gas: GO2 (air in 30% oxygen) and GN2O (the same mixture until the last 30 min of surgery, when 70% N2O in 30% oxygen was used). No PONV prophylaxis was given. Anesthesia was induced with thiopental 5 mg·kg-1, vecuronium 0.1 mg·kg-1, and fentanyl 1-2 µg·kg-1 iv and maintained with isoflurane. Indicators of early recovery (time to extubation, eye opening, following commands, orientation) were assessed by an anesthesiologist unaware of the group assignment. The incidence and severity of PONV was measured at two and 24 hr postoperatively. RESULTS: Altogether, 82 participants completed the study (42 in GO2, 40 in GN2O) and were analyzed. The mean (SD) time of N2O administration in GN2O patients was 27.1 (10.1) min. The mean (SD) time to extubation was faster in GN2O patients [5.4 (2.9) min] than in GO2 patients [7.5 (3.7) min] (mean difference, 2.0 min; 95% confidence interval [CI], 0.6 to 3.4, P = 0.009). The ability to open eyes, follow commands, and being oriented were all faster in GN2O patients than in GO2 patients (differences of 3.9 min, 95% CI, 1.6 to 6.1, P = 0.001; 3.4 min, 95% CI, 1.0 to 5.7, P = 0.006; 3.8 min, 95% CI, 0.9 to 6.7, P = 0.010, respectively). The incidence of PONV was not different between the groups, but the rescue antiemetic was required less often in the GN2O patients (mean difference in metoclopramide dose between the GN2O and GO2 groups, 5.1 mg; 95% CI, 0.8 to 9.4, P = 0.019). CONCLUSIONS: Adding N2O during the last 30 min of an isoflurane-based inhalational anesthetic reduced the time to extubation, eye opening, and orientation.

Transcranial Cerebral Oxymetric Monitoring Reduces Brain Hypoxia in Obese and Elderly Patients Undergoing General Anesthesia for Laparoscopic Cholecystectomy.

The aims of this prospective, observational study were to evaluate the changes of the regional cerebral saturation (rSO2) measured by near-infrared spectroscopy during elective laparoscopic cholecystectomy under total intravenous anesthesia and the association between patient's characteristics and critical decline of rSO2. Hemodynamics, rSO2, and oxygen saturation were recorded in different time points: before the anesthesia (Tbas), 2 minutes after the induction (supine position) (Tind), 2 minutes after CO2 insufflation (supine) (TCO2), 10 minutes after CO2 insufflation (reverse Trendelenburg) (TrevT), and 2 minutes after deflation (supine) (Tpost). Average age was 53±13 (range: 22 to 79 y). In 12 of a total of 62 patients (19.4%) the rSO2 decreased >20% (20.5% to 28.4%) in TCO2 or TrevT times. Significantly higher decrease of the rSO2 was found in patients older than 65 years and those with body mass index >30 kg/m (P<0.05). Noninvasive monitoring of cerebral oxygenation could be an important part of perioperative care in obese and older patients.

A case of Mediterranean spotted fever associated with severe respiratory distress syndrome.

Mediterranean spotted fever (MSF) is usually a mild endemic rickettsial disease occurring in southern Croatia. We have reported the clinical and epidemiological characteristics of an acute MSF case associated with severe respiratory distress syndrome and hemodynamical instability. The patient recovered completely after antimicrobial treatment. Indirect immunofluorescence assay (FOCUS Diagnostics Inc.) was performed to detect IgM and IgG antibodies to Rickettsia conorii. A significant increase of both IgM and IgG antibody titres found in paired acute- and convalescent-phase serum confirmed the diagnosis of acute MSF.

Metabolic syndrome increases risk for pulmonary embolism after hip and knee arthroplasty.

AIM: To investigate whether patients with metabolic syndrome (MetS) undergoing total hip or knee replacement have an increased risk for pulmonary embolism (PE). METHODS: We studied patients undergoing total hip or total knee replacement from January 2001 to April 2006. The diagnosis of PE was based on a positive finding with a chest CT or a lung scan. Components of MetS were defined as 1) BMI≥30 kg/m(2) , 2) non-fasting preadmission glucose ≥11.1 mmol/L or diagnosis of diabetes, 3) hypertension, and 4) dyslipidemia. MetS was diagnosed if at least three of these components were present. RESULTS: Of 7282 patients, 107 (1.47%) were diagnosed with PE. The incidence of PE in patients with 0, 1, 2, 3, and 4 MetS components was respectively 0.85% (16/1888; 95% confidence interval [CI] 0.5%-1.4%), 1.24% (31/2500; 95% CI 0.9%-1.8%), 1.76% (34/1936; 95% CI 1.2%-2.5%), 2.64% (21/796; 95% CI 1.7%-4.1%), and 3.09% (5/162; 95% CI 1.1%-7.4%). The independent risk factors for PE were age ≥70, knee as opposite to hip replacement, bilateral knee surgery, congestive heart failure, and MetS or the number of MetS components. The odds of PE independently increased 1.6 times (95% CI 1.01-2.56; P=0.043) for patients with MetS and 1.23 times (95% CI 1.02-1.48; P=0.028) per each additional MetS component. CONCLUSION: Patients with MetS are at increased risk for PE after total joint arthroplasty. The increasing number of MetS components significantly increased the incidence of PE.