Intravenous lipid emulsion as an antidote in clinical toxicology: a systematic review.

OBJECTIVE: Intravenous lipid emulsions (ILE) were developed many decades ago to supply nutritional requirements to patients unable to obtain adequate enteral nutrition. The utility of ILE was extended to therapeutics, facilitating the delivery of drugs. More recently, the potential for ILE to act as an antidote for inversion of drug toxicity has been recognized. This review aims to summarize the literature on ILE therapy as an antidote. Suggested mechanisms of action, safety profile, and recommendations on the administration of ILE in cases of drug intoxication are highlighted. MATERIALS AND METHODS: A complete literature survey was performed using the PubMed database search to collect available information regarding mechanisms of ILE action as an antidote, ILE administration for drug toxicity, and presentation of adverse events. RESULTS: A total of 102 studies met the selection criteria for inclusion in the review. Mainly used for local anesthetics toxicity, ILE therapy has been expanded in clinical toxicology involving overdose treatment of drugs other than local anesthetics. Partitioning in a lipid phase of fat droplets is a mechanism named the lipid sink phenomenon that has primarily been described to explain this action of ILE and remains the most widely accepted. At the same time, recent research has also revealed several molecular mechanisms that may contribute to ILE efficacy. CONCLUSIONS: ILE therapy comprises a recognized approach in clinical toxicology. Due to the lack of randomized clinical trials, recommendations on administration are based on animal studies and published cases. Thus, the constantly increased knowledge about ILE therapy supports the need for a detailed appraisal.

Views of cancer patients regarding cardiopulmonary resuscitation in Greece.

Cardiopulmonary resuscitation (CPR) in patients with cancer is an ethical issue of worldwide interest. A questionnaire-based study was carried out in a Greek oncology hospital aiming to explore the attitude of Greek cancer patients towards CPR. Overall, 200 patients (94 male, 106 female) of a mean age of 62.8 years took part in the study. Only 42 (21%) patients indicated that they knew what CPR really involves and only 20 (10%) patients thought that CPR has serious side effects, while the mean estimated in-hospital CPR survival rate to hospital discharge was 56.6% (minimum = 2%, maximum = 99%, standard deviation [SD] = 25.16) and 42.1% (minimum = 0%, maximum = 90%, SD = 24.56%) in case of unselected and cancer patients respectively. Despite their poor knowledge, 177 (88.5%) patients were willing to undergo CPR in case of an in-hospital arrest, 127 (63.5%) thought that they had the right to choose their CPR status and 141 (70.5%) believed that they should be asked about it when they enter the hospital. Most patients (36%) wanted their CPR status to be decided by themselves, their family and their doctor jointly. These findings indicate that specific measures should be applied to clinical practice in order to best manage this ethical issue, and consequently, improve cancer care.

The Chronic Pain Grade Questionnaire: validity, reliability and responsiveness in Greek chronic hip pain sufferers.

BACKGROUND: The Chronic Pain Grade Questionnaire (CPGQ) was developed to assess the global severity of chronic pain based on pain intensity and pain-related disability. This study aimed to translate, culturally adapt, and validate the Greek version of the CPGQ (CPGQ-Gr).  Methods: Adaptation into Greek followed established guidelines. We invited orthopedic outpatients suffering from chronic hip pain to participate in the study. The validity, reliability, and responsiveness of the CPGQ-Gr were assessed. RESULTS: Factor analysis yielded two factors (subscales), disability score (DS) and characteristic pain intensity (CPI). CPGQ-Gr items, total and subscale scores were highly correlated with the 12-Item Short Form Health Survey (SF-12) physical component summary score, and slightly correlated or not correlated with the SF-12 mental component summary score. Cronbach's alpha correlation coefficients for the CPGQ-Gr total scale, DS, and CPI subscales were 0.90, 0.95, and 0.83 respectively. All measures showed excellent temporal stability (intraclass correlation coefficients of 0.84, 0.92, and 0.91, respectively). Cliff's delta effect sizes ranged from 0.47 to 0.82. The values of the area under the receiver operating characteristic curve were consistent with good to excellent discriminatory ability (range: 0.747-0.902). CONCLUSION: Our findings suggest that the Greek version of the CPGQ is a valid, reliable, and sensitive to changes, instrument for grading the severity of chronic hip pain. HIPPOKRATIA 2018, 22(1): 37-42.

General versus neuraxial anaesthesia for caesarean section: impact on the duration of hospital stay.

We investigated retrospectively the duration of hospital stay of 1,619 women who received general (GA) (n = 582) or neuraxial anaesthesia (combined spinal-epidural [CSEA] (n = 614), epidural [EA] (n = 423)) for caesarean delivery over the years 2002-2005. Hospital stay was also analysed for the different obstetricians involved. Overall duration of hospital stay differed between 2002 and 2005 (p < 0.0001) but not between CSEA and EA (p = 0.460). Overall duration of hospital stay differed between neuraxial and GA group (p < 0.001). Duration of hospital stay of the GA group showed a progressive decrease between 2002 and 2005 (p = 0.002). Duration of hospital stay after neuraxial anaesthesia differed between 2002 and 2005 (p = 0.013) and among different surgeons (p < 0.001). Discharge rates from the hospital were shorter after neuraxial anaesthesia versus GA for the 3rd and 4th postoperative days (p < 0.001 and p < 0.001, respectively). Neuraxial anaesthesia for caesarean section seems to be associated with shorter duration of hospital stay than GA.

A randomized study of maternal serum cytokine levels following cesarean section under general or neuraxial anesthesia.

BACKGROUND: Cytokines are significant mediators of the immune response to surgery and also play a role in parturition. The aim of the study was to investigate the impact of the anesthetic technique for cesarean section on plasma levels of cytokines IL-6 and TNF-alpha. METHODS: Thirty-five parturients scheduled for elective cesarean section were randomly assigned to general (n=18) or neuraxial (n=17) anesthesia. The general anesthesia group received thiopental 4 mg/kg, succinylcholine 1-1.5 mg/kg and 1% end-tidal concentration of sevoflurane in nitrous oxide and 50% oxygen. The neuraxial anesthesia group received intrathecal 0.5% levobupivacaine 1.8-2.2 mL and epidural fentanyl 1 microg/kg. Blood samples were taken for IL-6 and TNF-alpha immediately after positioning the parturient on the operating table, after uterine incision and before the umbilical cord clamping and 24h after surgery (T(1), T(2) and T(3) respectively). RESULTS: The two groups did not differ in IL-6 (P=0.15) or TNF-alpha (P=0.73) serum concentrations at any time point. In the general and neuraxial anesthesia groups, IL-6 serum concentrations were significantly higher in the third blood sample, T(3) (12.2+/-5.0 and 15.2+/-4.3 pg/mL), than in T(1) (0.41+/-0.38 and 0.29+/-0.10 pg/mL) and T(2) (0.37+/-0.47 and 0.24+/-0.05) respectively (P<0.001). Within each group, serum TNF-alpha concentrations did not differ significantly over time (P=0.44). CONCLUSIONS: Under the present study design anesthetic technique did not affect IL-6 or TNF-alpha concentrations in parturients undergoing elective cesarean section. Serum IL-6 levels increased 24 h postoperatively independently of anesthetic technique.

Local application of halothane, isoflurane or sevoflurane increases the response to an electrical stimulus in humans.

UNLABELLED: Volatile anesthetics may interfere with pain perception. This study investigates the effect of halothane, isoflurane and sevoflurane when applied locally, to the response of an electrical stimulus. METHODS: In this randomized control double-blind crossover study 70 volunteers were studied. In experiment 1 (30 subjects), equipotent liquid volumes of halothane 1 ml, isoflurane 1.5 ml and sevoflurane 2.7 ml were randomly applied on one forearm for 30 minutes. The other forearm received water. Both forearms were exposed to an electrical stimulus. The experiment was repeated the following day in a reverse fashion. In experiments 2 (20 subjects) and 3 (20 subjects) the response to the same stimulus was tested after local application of 2, 4, and 6 ml of halothane or 5 ml of sevoflurane respectively. RESULTS: Low doses of the three anesthetics were associated with an increased response to the electrical stimulus (F = 8.940, df = 1,174, P = 0.003). Higher doses of halothane and sevoflurane had no effect on the response (F = 2.358, df = 1,114, P = 0.127 and t = 0.840, df = 19, P = 0.411 respectively). CONCLUSIONS: Low liquid volumes of volatile anesthetics, when applied locally to the skin enhanced the response to an electrical stimulus but higher volumes had no effect.

Responses to mechanical and electrical stimuli are not attenuated by late pregnancy.

Pregnancy has been associated with increased pain threshold. This study investigates the responses to mechanical and electrical stimuli in pregnant and non-pregnant women. Thirty pregnant women were subjected before and four days after elective caesarean section under regional anaesthesia to mechanical and electrical stimuli on both forearms. Thirty nonpregnant women were subjected to the same stimuli at the same time points. The responses to mechanical stimuli were expressed in mm of the Visual Analogue Scale (VAS) and averaged for both forearms. The VAS scores obtained after the electrical stimuli were divided by the mA recorded when the stimulus was applied, expressed in mm/mA and averaged. The responses to mechanical stimuli recorded before and four days after application did not differ between the two groups (F = 0.884, df = 3,116, P = 0.452). In the pregnant group the VAS values before and four days after the caesarean section were 16.4 +/- 14.4 mm and 12.8 +/- 12.5 mm respectively. In the nonpregnant group the VAS values recorded four days apart were 17.5 +/- 14.3 mm and 13.4 +/- 11.9 mm respectively. The responses to electrical stimuli applied four days apart also did not differ between the two groups (F = 2.433, df = 3,116, P = 0.069). The VAS values obtained after the first and second application of the electrical stimulus were 0.914 +/- 0.606 mm/mA versus 0.586 +/- 0.410 mm/mA in the pregnant and 0.853 +/- 0.538 mm/mA versus 0.725 +/- 0.467 mm/mA in the nonpregnant group. These results, under the study conditions, do not support the hypothesis that late pregnancy is associated with increased antinociception in humans.

Sevoflurane as a single anesthetic and physostigmine failure to enhance arousal.

AIM: Sevoflurane is recommended for inhalational induction of anesthesia. Physostigmine may antagonize general anesthetics. The study investigates sevoflurane as a single anesthetic and its possible antagonism by physostigmine. METHODS: In 60 women scheduled for breast lump excision, anesthesia was induced with 8% sevoflurane. After 3 min of sevoflurane inhalation, a laryngeal mask airway (LMA) was inserted. Anesthesia was maintained with spontaneous ventilation at end tidal sevoflurane 3%. Systolic and diastolic blood pressure, heart rate and end tidal CO(2) were recorded intraoperatively. After skin closure and at end tidal sevoflurane 0.9%, physostigmine 2 mg or normal saline was given. After 2 min systolic, diastolic blood pressure, heart rate and end tidal CO(2) were recorded and sevoflurane was discontinued. Time to eyes opening, LMA removal and verbal response was recorded. Patients were also assessed for orientation, sedation, sitting ability and the ''picking up matches'' test at 0, 15 and 30 min after LMA removal. RESULTS: Systolic, diastolic blood pressure and heart rate increased after laryngeal mask placement (P=0.0001, P=0.0001 and P=0.0001, respectively). Orientation, sitting ability and ''picking up'' matches were similar in the 2 groups. Sedation at 15 min was less in the control group (P=0.004). CONCLUSIONS: Sevoflurane can be used as a single anesthetic but its recovery is not enhanced by physostigmine.

Gabapentin attenuates late but not acute pain after abdominal hysterectomy.

BACKGROUND AND OBJECTIVE: Gabapentin has been suggested to decrease acute postoperative pain. We evaluated the effect of gabapentin on pain after abdominal hysterectomy. METHODS: Sixty patients scheduled for abdominal hysterectomy were randomized to receive orally gabapentin 400 mg 6 hourly or placebo. Treatment started 18 h preoperatively and continued for 5 postoperative days. Pain (visual analogue score) and consumption of morphine for 48 h and of oral paracetamol/codeine were recorded after 2, 4, 8, 24 and 48 h and on days 3-5 postoperatively. After 1 month, patients were interviewed by phone for pain, and analgesic intake after hospital discharge. RESULTS: Morphine consumption (mean +/- SD) was 35 +/- 15.7 mg in the control and 28 +/- 12.1 mg in the gabapentin group (P = 0.21). Median number (range) of paracetamol 500 mg/codeine 30 mg tablets taken during days 3-5 was 1.0 (0-6) in the control and 2.0 (0-9) in the gabapentin group (P = 0.35). The visual analogue scores at rest and after cough did not differ between the two groups (F = 0.92, df = 1, P = 0.34 and F = 0.56, df = 1, P = 0.46, respectively). One month after surgery, 22/27 (81%) of the control group and 9/25 (36%) of the gabapentin group reported pain in the surgical area (chi(2) = 11.15, P = 0.002), while 11/27 (41%) of controls and 7/25 (28%) of gabapentin patients consumed analgesics for pain (chi(2) = 0.93, P = 0.39). The intensity of pain was decreased in the gabapentin group (chi(2) = 12.6, P = 0.003). CONCLUSIONS: Gabapentin has no effect on immediate pain after abdominal hysterectomy but decreases pain 1 month postoperatively.

Spread of subarachnoid block, intraoperative local anaesthetic requirements and postoperative analgesic requirements in Caesarean section and total abdominal hysterectomy.

BACKGROUND: Pregnancy is associated with a higher spread of subarachnoid anaesthesia and increased pain threshold. The study was designed to assess the spread of subarachnoid block and the intra- and postoperative analgesic requirements in pregnant vs non-pregnant women. METHODS: We assessed the level of subarachnoid anaesthesia after 1.8 ml of hyperbaric lidocaine 5% and the postoperative analgesic requirements in women undergoing Caesarean section and undergoing abdominal hysterectomy (30 each group). Intraoperatively epidural ropivacaine was given as required. All patients received 10 ml of ropivacaine 0.2% epidurally 2, 10, and 24 h after operation and the VAS pain score was assessed. They also had access to patient controlled analgesia i.v. morphine. RESULTS: Duration of surgery was 64 (13.7) vs 127 (33.8) min (P<0.0001) in the pregnant and non-pregnant groups. Ten minutes after subarachnoid injection, sensory block was higher by three dermatomes in the pregnant group (P<0.0001). Time to first ropivacaine dose was 37 (19.7) vs 19 (12.2) min (P<0.001) and the ropivacaine normalized for the duration of anaesthesia was 0.8 (0.6) vs 1.3 (0.5) mg(-1) (P=0.001) in the pregnant and non-pregnant groups, respectively. The time between the first and second ropivacaine dose was similar in the two groups (P=0.070). Fewer pregnant women (81 vs 100%) required ropivacaine intraoperatively (P=0.017). The VAS scores were similar but parturients consumed more i.v. morphine (33 (14) vs 24 (12) mg, P=0.016) during the first 24 h after operation. CONCLUSIONS: Pregnant patients exhibited a higher level of subarachnoid sensory block and required more i.v. morphine after operation.

Pharmacokinetic profile and efficacy of a fentanyl transdermal delivery system for acute postoperative pain after intra-abdominal gynecologic surgery for cancer.

PURPOSE: This prospective, randomized, single-blind study evaluated the efficacy and pharmacokinetic profile of a transdermal delivery system for fentanyl to provide relief of acute postoperative pain in patients undergoing intra-abdominal gynecologic surgery for cancer. METHODS: Forty female patients were randomized to either transdermal fentanyl 50 microg/hour (n = 20) or transdermal placebo (n = 20). Transdermal systems were placed 1 hour preoperatively and removed 25 hours later. Pain control was supplemented with a nonopioid drug, bupivacaine 0.125-0.25%, administered through an epidural catheter via patient-controlled epidural analgesia. Serum fentanyl concentrations, bupivacaine consumption, pain scores [visual analog scale (VAS)], sedation rating score, adverse events, and physiological parameters were recorded for 48 hours postoperatively. RESULTS: The minimum effective concentration of fentanyl in serum (0.63 ng/mL) was achieved at 11.3 +/- 4.9 hours after application, and serum concentrations remained above this level until 13 hours after removal. The TTS-F group had lower VAS pain scores and a significant 66% reduction in utilization of bupivacaine compared with placebo. Pain scores were significantly correlated with serum fentanyl concentration (P = 0.025). All physiological parameters fluctuated within normal range and no differences were observed between treatments. Adverse events were similar between the groups with only the incidence of local erythema significantly higher in the TTS-F group (30% vs. 5%, P < 0.05), and sedation scores were significantly higher in the TTS-F group during the immediate postoperative period. CONCLUSION: The transdermal therapeutic system for administration of fentanyl, combined with epidural administration of a nonopioid analgesic such as bupivacaine is effective in controlling postoperative pain after gynecologic surgery. Additionally, the safety/tolerability of this regimen was similar to placebo plus bupivacaine.

Needling of the extra 1 point decreases BIS values and preoperative anxiety.

Acupuncture has anxiolytic effects. We investigated the effect of acupuncture on the Bispectral Index (BIS) values and anxiety. Fifty patients were randomly assigned to group A to receive acupuncture for 15 minutes on the extra 1 point (yintang) or to group C, where they received the same treatment on a control point located 2 cm lateral to the end of the right eyebrow. BIS values were recorded before acupuncture; during acupuncture every 30 seconds for 15 minutes and every 30 seconds for 90 seconds when the acupuncture treatment was accomplished. Anxiety level was assessed before and after acupuncture by a verbal score scale (VSS) (0 = no anxiety, 10 = worst anxiety). BIS values were significantly decreased during acupuncture when applied on the extra 1 point (p = 0.0001) but not on the control point. Acupuncture application significantly decreased the VSS values within the A group (p = 0.027) and in the C group (p = 0.0001), when compared to the baseline (pre-acupuncture) VSS values. However, no differences were found between the two groups regarding BIS or VSS values. In conclusion, needling the extra 1 point preoperatively significantly decreases the BIS values and the VSS for anxiety but needling of a control point decrease only VSS values.

Direction and side used to determine the extent of sensory block after subarachnoid anesthesia do not influence the level of the block.

Methods of sensory testing in neuraxial anesthesia may supposedly account for different results in reporting the extent of the block. To determine whether the caudad to cephalad versus the cephalad to caudad direction as well as the side of testing, left versus right, may affect the assessment of sensory block after subarachnoid anesthesia, two groups of patients undergoing transurethral surgery were studied. One group, 44 patients were tested for the influence of direction of block determination and another group 50 patients for the influence of side. Subarachnoid anesthesia was performed with 100 mg of 5% hyperbaric lidocaine using a 25 Whitacre needle with its opening consistently pointing cranially and the patient in the sitting position. To assess the sensory block four lines were drawn bilaterally along the posterior, middle, and anterior axillary lines and a line 5 cm medial to the anterior axillary line. A pressure palpator was moved along each of the four lines and patients were asked to answer if they detected a stimulus, with "yes/no". In the 44 patients assessment of sensory block was performed from caudad to cephalad direction on one side and viceversa on the other. In the other 50 patients the extent of the block was compared between the right and left side. In 44 patients, the level of sensory block determined 20, 25 and 30 minutes after the subarachnoid anesthesia in a cephalad to caudad direction was found at the T11 dermatome at each time point and did not differ when compared to the levels determined following the caudad to cephalad direction. In the second study in a different group of 50 patients, the level of sensory block 20, 25 and 30 minutes after the subarachnoid injection was found at the T11 dermatome on the right side at each time point and did not differ from the level determined on the left side. We conclude that the level of sensory block after subarachnoid anesthesia with lidocaine is independent of the direction of testing and the side the assessment is performed using the pressure palpator.

Accidental epidural injection of vecuronium.

IMPLICATIONS: We report a case of accidental epidural injection of vecuronium in a female patient who underwent hemorrhoidectomy using epidural anesthesia. Because epidural injection of muscle relaxants may have serious side effects, immediate establishment of airway protection, monitoring of muscle relaxation, and follow-up for clinical signs of neurotoxicity are recommended.

Renin-aldosterone system alterations during abdominal gynaecological operations under general or combined general and epidural anaesthesia.

Alterations of plasma renin-activity and aldosterone levels were comparatively studied in 41 premenopausal patients who were subjected to total abdominal hysterectomy. Twenty-one women received general anaesthesia (group A) and 20 received a combination of general and epidural anaesthesia (group B). Five blood specimens were drawn from each patient in order to determine plasma aldosterone levels (PA) and plasma renin activity (PRA) by radioimmunoassay (RIA). The rise of PA levels in group A occurred 30 min after the initiation of surgery and at that time there was a statistically significant difference as compared with the epidural anaesthesia (EA) group (p < 0.001). PRA levels in both groups showed a rise of limited statistical significance at 30 minutes after the initiation of surgery (p < 0.05). During the remaining time intervals, group A did not show any significant changes, whereas group B showed a reduction of limited statistical significance (p < 0.05). General anaesthesia for gynecological abdominal surgery without the use of volatile agents significantly increases plasma aldosterone levels. Combined anaesthesia does not totally inhibit intraoperative hyperaldosteroism but it is much slower and is of great advantage for the patient.

Modulation of synaptosomal plasma membrane-bound enzyme activity through the perturbation of plasma membrane lipid structure by bupivacaine.

UNLABELLED: We investigated modulations of lipid dynamics and lipid-protein interactions of rat brain synaptosomal plasma membrane (SPM) as one of the possible mechanisms by which the local anesthetic bupivacaine (BPV) has an adverse effect on nerve cell function, with SPM-bound enzyme activity used as a functional probe. The kinetics of BPV impact on the activity of the endoenzymes Ca2+/Mg2+-stimulated ATPase and Na+/K+-stimulated ATPase and the active concentrations of the drug were relevant to those that produce biphasic systemic toxicity. Arrhenius plots of these enzymes showed a transition temperature of 26.6 +/- 1.8 degrees C and 24.5 +/- 1.2 degrees C (mean +/- SD), respectively, in control SPM, which shifted to 17.1 +/- 0.95 degrees C (P < 0.01) and 18.2 +/- 0.85 degrees C (P < 0.05) in SPM treated with 10(-5) M BPV. The Hill coefficients for the allosteric inhibition of Ca2+/Mg2+-stimulated ATPase by Na+ and Na+/K+-stimulated ATPase by fluoride decreased from 1.73 +/- 0.20 and 1.95 +/- 0.25, respectively, in controls to 0.92 +/- 0.09 (P < 0.001) and 1.09 +/- 0.11 (P < 0.001) in the presence of 10(-5) M BPV. The fluidity perturbation in the microenvironment of the ectoenzyme acetylcholinesterase was observed only at 5 x 10(-3) M BPV, as confirmed by the disparity in transition temperature between the controls (22.3 +/- 1.2 degrees C) and the BPV-treated SPM (17.5 +/- 0.8 degrees C, P < 0.01) and that in the Hill coefficient in the two groups: 2.15 +/- 0.24 and 0.97 +/- 0.12 (P < 0.001), respectively. IMPLICATIONS: We propose that under physiological conditions, the neutral and protonated forms of local anesthetics can affect nerve cell function through the asymmetric perturbation of the membrane lipid structure, accompanied by synaptosomal plasma membrane-bound enzyme dysfunction.

A comparative study of propofol and thiopental as induction agents for elective caesarean section.

Twenty women for elective caesarean section received either propofol 2.3 mg/kgr or thiopental 4.4 mg/kgr for induction of general anaesthesia. Maintainance was similar for both groups. Mean arterial pressure and heart rate were recorded non-invasively before anaesthesia, during intubation, one and five minutes after intubation. There were no significant differences in haemodynamic response between the two groups. During intubation heart rate rose in both groups, but remained increased five minutes after tracheal intubation only in the thiopental treated women (p less than 0.05). There was no significant neonatal depression as assessed by Apgar Scores and blood gas analyses. Propofol appears to be a suitable alternative to thiopental as an induction agent for obstetric anaesthesia.