Evaluation of the Effectiveness of Sugammadex for Digoxin Intoxication: An Experimental Study.

Previous studies have shown that cyclodextrin group medicines bind to various drugs. The hypothesis of our study is to determine whether sugammadex could bind to digoxin and delay the cardiovascular toxicity of that drug. Twenty-eight sedated Wistar rats were infused with digoxin at 3 mg/h (0.25 mg/ml). Five minutes after the start of infusion, animals were treated with a bolus of either 16 mg/kg (Sgdx16), 100 mg/kg (Sgdx100), or 1000 mg/kg (Sgdx1000) sugammadex. The control group infusion did not contain sugammadex. Heart rate, electrocardiography, and respiratory rate were monitored. The primary endpoint was time to asystole. Digoxin infusion continued until the animals arrested. The time to asystole for the Sgdx1000 group was significantly longer compared to that for the control group (p < 0.05). The mean lethal dose of digoxin was 5.35 ± 2.06 mg/kg in the saline-treated rats. On the other hand, the mean lethal dose of digoxin was 8.54 ± 1.51 mg/kg in the sugammadex 1000 group (p < 0.05). The mean lethal dose of digoxin was significantly higher than control group (p < 0.05). We found that the 1000 mg/kg dose of sugammadex delayed digoxin cardiotoxicity in a rat model of digoxin toxicity. We conclude that further research must be conducted on the interaction between digoxin and sugammadex.

Day-Time Isoflurane Administration Suppresses Circadian Gene Expressions in Both the Brain and a Peripheral Organ, Liver.

OBJECTIVE: The aim of this study is to investigate the effects of light and administration time of isoflurane on circadian gene expression in the brains and liver tissues of rats kept in light-dark cycle. METHODS: Seventy two 15-days-old rats pups were divided into four groups. All animals were exposed to 1.5% concentration of isoflurane or to 6 L min-1 O2 for six hours between Zeitgeber Time (ZT) 0-ZT06 (day-time administration) or ZT12-ZT18 (night-time administration). Rats were sacrificed after six hours of anaesthesia with four-hour time intervals. Total RNA was isolated from brains and liver tissues. Circadian gene expression was examined using quantitative real-time Reverse transcription polymerase chain reaction (RT-PCR). RESULTS: BMAL1, CLOCK, PER2 and CRY2 gene expression levels were markedly suppressed after day-time anaesthesia in the both brain and liver, but night-time administration caused only temporary suppression of gene expression. CONCLUSION: The effect of isoflurane on the circadian clock is time-dependent, and administered isoflurane anaesthesia at night had minimal effect on clock gene expression. Additionally, when the treated animals were kept in a regular light-dark cycle, isoflurane-induced phase shift was not observed, possibly because of the light.

What are the hemodynamic and respiratory effects of passive limb exercise for mechanically ventilated patients receiving low-dose vasopressor/inotropic support?

Passive limb exercises (PLEs) are used widely in the management of unconscious patients and an early start is recommended. The aim of this study was to determine the effects of PLEs on hemodynamic and respiratory parameters in mechanically ventilated critically ill patients receiving low-dose vasopressor/inotropic support. The charts of 120 mechanically ventilated patients who underwent PLEs were evaluated retrospectively between January 2000 and July 2002. Patients were grouped on the basis of administration of vasopressor/inotropic support. Thirty-eight patients did not get vasopressor/inotropic support (group 1) and 82 patients received low-dose vasopressor/inotropic support (dopamine <10 µg/kg/min, noradrenaline/adrenaline <0.1; group 2). Central venous pressure, heart rate, mean arterial pressure, and oxygen saturation were recorded before and immediately after PLEs. After PLEs in group 1 patients, central venous pressure and mean arterial pressure values increased significantly, and in group 2 patients, central venous pressure increased significantly (P < .05). No statistically significant difference was observed in the rate of change of hemodynamic or respiratory parameters between the 2 groups after the PLEs (P > .05). This retrospective study confirmed that PLEs result in similar hemodynamic and respiratory changes in critically ill patients who received low-dose vasopressor/inotropic support versus those who do not.

Evaluating the Readibility of Informed Consent Forms Available Before Anaesthesia: A Comparative Study.

OBJECTIVE: Informed consent forms that are used prior to administering anaesthesia inform patients before any proposed surgical procedure or treatment. They should provide patients with sufficient information about the operation and treatment. Readibility refers to whether it is easy or hard for a reader to read and understand an available text, and this is evaluated via various formulas. The aim of this study was to evaluate the readability of different informed consent forms commonly used in the anaesthesiology departments of different hospitals in our country using different readability formulas. METHODS: After obtaining ethics committee approval, the readability of different consent forms used in the anaesthesiology departments of university hospitals (n=15), Ministry of Health (MOH) education and research hospitals (n=15), and public hospitals (n=15) was analysed. Each consent form was displayed electronically in "Microsoft Word" and the number of words contained was counted automatically. The first 100 words on the first page of the forms were evaluated using the Gunning Fog, Flesch-Kincaid and Atesman readability formulations. The rate of medical terms detected within these 100 words was determined as a percentage (%). RESULTS: Different consent forms obtained from 45 anaesthesia departments were assessed using various readability formulas. According to the Gunning Fog index, the readability of the consent forms obtained from MOH education and research and public hospitals was relatively low. The Flesch-Kincaid index measured very low levels of readability in all institutions. The Atesman index displayed very low readability levels for the consent forms used in university hospitals, and low levels in other institutions. CONCLUSION: We conclude that the readability of the anaesthesia informed consent forms is low. The level of education in our country should be considered in the preparation of anaesthesia consent forms. We believe that physicians should pay more attention to this medical and legal issue.

Evaluation of the effectiveness of sugammadex for verapamil intoxication.

Previous studies have shown that medications from the cyclodextrin family bind to verapamil. The aim of our study was to determine whether sugammadex could bind to verapamil and prevent the cardiovascular toxicity of that drug. Twenty-eight sedated Wistar rats were infused with verapamil at 37.5 mg/kg/h. Five minutes after the start of infusion, the animals were treated with a bolus of either 16 mg/kg, 100 mg/kg or 1000 mg/kg sugammadex. The control group was treated with an infusion without sugammadex. The heart rate and respiratory rate were monitored, and an electrocardiogram was recorded. The primary end-point was the time to asystole. The verapamil infusion continued until the animals arrested. The asystole time for the S16 group was significantly longer compared to those for the control and S1000 groups (p < 0.05). The asystole time for the S1000 group was significantly shorter than those for all of the other groups (p < 0.05). Reflecting these data, there was a near doubling of the mean lethal dose of verapamil from 13.57 mg/kg (S.D. ±8.1) in the saline-treated rats to 22.42 mg/kg (S.D. ±9.9) in the sugammadex 16 group (p < 0.05). However, for the sugammadex 1000 group, the mean lethal dose was found to be 6.28 ± 1.11 mg/kg. This dose is significantly lower than those for all of the other groups (p < 0.05). We found that treatment with 16 mg/kg sugammadex delayed verapamil cardiotoxicity in rats. However, 1000 mg/kg sugammadex accelerated verapamil cardiotoxicity in rats. Further studies must be conducted to investigate the interaction between verapamil and sugammadex.

Respiratory and hemodynamic responses to mobilization of critically ill obese patients.

PURPOSE: The aim of this study was to investigate the effects of mobilization on respiratory and hemodynamic parameters in critically ill obese patients. METHODS: Critically ill obese patients (n = 31) were included in this retrospective study. Data were collected from patients' files and physiotherapy records of mobilization sessions. Heart rate (HR), systolic/diastolic/mean blood pressure, respiratory rate (RR), and percutaneous oxygen saturation (SpO(2)) were recorded. Cardiorespiratory parameters were collected just prior to the mobilization, just after the completion of the mobilization and after 5 minutes recovery period. Respiratory reserve was calculated before and after the mobilization. RESULTS: A total of 37 mobilization sessions in 31 obese patients (mean age: 63.3 years, mean BMI: 32.2 kg/m(2)) who received physiotherapy were analyzed. Respiratory rate increased significantly after the completion of the mobilization compared to initial values (p < 0.05). SpO(2) significantly increased (p < 0.05) and all other parameters remained similar (p > 0.05) compared to initial values after the recovery period. Mobilization resulted in a significant increase in respiratory reserve (p < 0.05). CONCLUSION: Early mobilization in intensive care unit promotes respiratory reserve in obese patients. We found that mobilization can be performed safely in critically ill obese patients if cardiorespiratory parameters are continuously monitored.

Comparison of the effects of 2 different doses of remifentanil infusion for sedation during in-vitro fertilization procedure.

OBJECTIVE: To compare the sedation level, hemodynamic effects, patient and physician satisfactions following sedation achieved by 2 different doses of remifentanil (R) infusion with additional bolus infusions of propofol for in vitro fertilization (IVF) procedure. METHODS: A double-blind prospective randomized study was implemented on 86 ASA I-II grade female patients, 18-40 years of age that underwent IVF procedure. This study was performed in the Department of Anesthesiology and Obstetrics and Gynecology, School of Medicine, Dokuz Eylul University, Izmir, Turkey between November 2006 to August 2008. Group R1 received 0.1 mcg/kg/min while Group R2 received 0.15 mcg/kg/min infusion dose remifentanil. Side effects, total doses of remifentanil and propofol administered, heart rate (HR), systolic arterial pressure and diastolic arterial pressure values have been recorded. Fertilization, cleavage, and pregnancy rates together with prognosis of pregnancies were compared. RESULTS: Groups did not show statistically significant differences for hemodynamic parameters of HR and MAP (p = 0.281). Comparison of the satisfaction levels of 2 groups showed that anesthesiologist satisfaction was superior in R1 (p = 0.009) whereas surgeon satisfaction was superior in R2 (p = 0.01). Both groups reported good patient satisfaction levels (p = 0.31). There were no differences between the groups in terms of fertilization, cleavage, pregnancy rates and prognosis of pregnancies (p>0.05). CONCLUSION: Both doses of remifentanil provided stable hemodynamics along with fast and uncomplicated recovery.

Haemodynamic effects of physiotherapy programme in intensive care unit after liver transplantation.

OBJECTIVE: To determine the haemodynamic effects of intensive care physiotherapy after liver transplantation. PATIENTS AND METHODS: Thirteen patients were included in the study after liver transplantation. The following physiotherapy programme were applied to the patients in intensive care unit: Respiratory physiotherapy, active joint movements, sitting in bed (first task), sitting at the edge of bed (second task), standing (third task), sitting out of bed (fourth task) and walking (fifth task). Heart rate (HR), mean, systolic and diastolic blood pressures (MBP, SBP, DBP), peripheral oxygen saturation (SpO(2)), respiration rate (RR) were recorded before treatment, after each task, after treatment and at the fifth minute of recovery. Pain level was assessed with Visual Analogue Scale (0-10). RESULTS: When compared with supine position before treatment, all of the parameters except RR increased after the first task whereas HR, SBP, MBP and pain increased after the second task. After the third task only HR and pain increased. There was no significant difference between the fourth task and pre-treatment values while HR, DBP and pain increased after the fifth task. When measurements of pre-treatment, immediately after treatment and the fifth minute of recovery were compared HR, MBP and pain increased after treatment whereas HR, RR and pain decreased after recovery. There was no significant difference between pre-treatment values and fifth minute of recovery measurements. CONCLUSION: Returning to initial values after a 5-min period shows that cardiopulmonary changes caused by intensive care physiotherapy after liver transplantation are responded at physiological limits.

A cross-over, post-electroconvulsive therapy comparison of clinical recovery from rocuronium versus succinylcholine.

STUDY OBJECTIVE: To evaluate the effect of the neuromuscular blocking agent, rocuronium, on clinical recovery from electroconvulsive therapy (ECT) as compared with succinylcholine. DESIGN: Cross-over study. SETTING: University hospital. PATIENTS: 13 ASA physical status I and II patients, ages 18 to 60 years, receiving ECT three times a week. INTERVENTIONS: Each patient received either succinylcholine before the first ECT session (Group S) and rocuronium before the third ECT session (Group R). Muscle paralysis was produced with succinylcholine one mg kg(-1) intravenously (IV) or rocuronium 0.3 mg kg(-1) IV. Reversal of the residual neuromuscular block (Group R) was accomplished with 10 microg kg(-1)of atropine and 20 microg kg(-1)of neostigmine after completion of the ECT procedure. MEASUREMENTS: Motor seizure duration time, time to first spontaneous breathing, eye opening, head lift, and tongue depressor test were recorded. MAIN RESULT: Motor seizure duration and time to first spontaneous breath was longer (33.6 sec vs. 24.2 sec; 9.46 min vs 8.07 min, respectively) in the rocuronium group than the succinylcholine group. No significant difference was detected between the two groups in eye opening, head lift, or tongue depressor testing. CONCLUSION: Rocuronium, when used in conjunction with a reversal agent, may be an adequate alternative to succinylcholine as a neuromuscular blocker during ECT.

Effect of deep breathing exercises on oxygenation after major head and neck surgery.

OBJECTIVES: To investigate respiratory and hemodynamic responses to deep breathing exercise (DBE) during the follow-up period in the intensive care unit after major head and neck surgery. STUDY DESIGN: Prospective study. SUBJECTS AND METHODS: Thirty-five patients were instructed to perform DBE every hour for 3 consecutive hours during the first postoperative day. The ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO(2)/FiO(2)), oxygen saturation (SpO(2)), respiratory rate (RR), heart rate (HR), and mean arterial pressure (MAP) was recorded. RESULTS: DBE increased the PaO(2)/FiO(2) ratio from 416.7 +/- 143.6 to 453.4 +/- 141.4 mm Hg and increased SpO(2) from 97.4 +/- 1.9 to 99.2 +/- 0.9. DBE decreased the RR from 24.1 +/- 3.3 to 21.8 +/- 2.9 breaths/min (P < 0.05). No statistically significant difference in HR or MAP was observed after DBE (P > 0.05). CONCLUSION: DBE improves oxygenation after major head and neck surgery, without causing additional harmful hemodynamic effects.

Comparison of the effectiveness of pretreatment by fentanyl and remifentanil on rocuronium induced injection pain.

OBJECTIVE: To compare the efficacy of fentanyl and remifentanil as prodrugs in the prevention of rocuronium injection pain by using a control group. METHODS: In a randomized, double-blinded, controlled study, 102 adult patients aged between 18-60 undergoing elective surgery under general anesthesia and classified into American Society of Anesthesiologists (ASA) I and ASA II risk groups were included in the study. The study was carried out from July 2005 to April 2006 at Dokuz Eylul University, Izmir, Turkey. Unpremedicated patients were randomly allocated to one of 3 groups. Patients received 2 mL (0.02 mg) of remifentanil (n =34), 2 mL of fentanyl 0.1 mg (n =34), and 2 mL of saline (n =34), by injection over 10 seconds. Thirty seconds after prodrug administration, 10 mg (10 mg/mL) intravenous rocuronium bromide was administered over 5 seconds and pain assessment was performed by using a 5-point scale. RESULTS: When the 3 groups of 34 patients were compared in terms of pain assessment scoring, a statistically significant difference was determined (p=0.02). When the groups were paired, it was seen that this difference resulted from the remifentanil and saline groups (p=0.02). CONCLUSION: This study shows that a bolus dose of 0.02 mg of remifentanil is a more effective prodrug administration compared to the application of saline, however, remifentanil and fentanyl have no superiority over one another and the administration of fentanyl is equally effective as saline prodrug administration.

Neuroprotective effects of ketorolac tromethamine after spinal cord injury in rats: an ultrastructural study.

INTRODUCTION: The aim of this study was to investigate the effects of intrathecally administered ketorolac tromethamine on ultrastructural changes of the spinal cord in spinal cord-traumatised rats. METHODS: Male Wistar rats were used and divided into three groups for this study. The rats in Group S (n=6) were control animals and received 10 mul of saline. Groups K50 (n=6) and K400 (n=6) received intrathecally 50 mug and 400 mug of ketorolac tromethamine, respectively, immediately after trauma was induced. All rats underwent laminectomy and the spinal cord was traumatised using the clip-compression technique. Electron microscopic examination of the cord samples was carried out 3 days after spinal cord injury. RESULTS: Ultrastructural findings showed severe injury with extensive axoplasmic and cytoplasmic oedema in Group S. Minor neural damage occurred in Group K50 and increased ultrastructural protection was observed in the Group K400. CONCLUSION: This study demonstrates that intrathecal administration of ketorolac tromethamine protects the spinal cord following injury in rats.

The effects of alfentanil or remifentanil pretreatment on propofol injection pain.

STUDY OBJECTIVE: To compare the efficacy of alfentanil, remifentanil, and saline in minimizing the propofol injection pain. DESIGN: Randomized, double-blind study. SETTING: University hospital. PATIENTS: 175 ASA physical status I and II, adult female patients undergoing minor gynecological procedures with general anesthesia. INTERVENTIONS: Unpremedicated patients were randomly allocated to one of four groups. Patients received 2 mL (1 mg) of alfentanil (n=43), 2 mL of remifentanil 0.01 mg (n = 43), 2 mL of remifentanil 0.02 mg (n=45), or 2 mL of saline (n=44) 30 seconds prior to administration 5 mL of propofol 1%. MEASUREMENTS: Patients were asked whether they had pain due to propofol injection. Their pain scores were evaluated with a Visual Analogue Scale. In the Postanesthesia Care Unit, frequency of postoperative nausea, vomiting, hypotension, and flushing were all determined. MAIN RESULT: The remifentanil and alfentanil groups showed significantly less frequency and severity of pain than the saline group (p <0.05). When the alfentanil group was compared with the remifentanil groups, significant differences in pain relief associated with injection of propofol (p <0.001) were noted. Remifentanil 0.02 mg relieved pain associated with injection of propofol more effectively than remifentanil 0.01 mg (p <0.001). CONCLUSIONS: The remifentanil and alfentanil groups showed significantly less frequency and severity of pain than did the saline group. Remifentanil was effective in preventing propofol injection pain, and should be used at a dose of at least 0.02 mg for this purpose. Remifentanil may be an alternative drug for prevention of propofol injection pain.

Antinociceptive and neurotoxicologic screening of chronic intrathecal administration of ketorolac tromethamine in the rat.

UNLABELLED: Many drugs are tested intrathecally to investigate alternatives to opioids. We aimed to explore the analgesic and possible neurotoxic effects of chronic intrathecally-administered ketorolac tromethamine in rats. Catheters were placed via atlantoaxial interval in 28 Wistar rats under anesthesia of intraperitoneally-injected thiopental 30 mg/kg. Rats were randomized into 4 groups and administered 4 repeated intrathecal doses of therapy with 5-day intervals. The control group received 10 microL of saline, and the other groups received 50, 150, and 400 microg of ketorolac tromethamine respectively. The formalin test, behavioral test, and histopathological examination of four different spinal cord levels were performed. Neither behavioral testing nor histopathological examination revealed abnormalities that would suggest neurotoxicity. Formalin tests showed that both phase I and phase II responses of ketorolac tromethamine groups were significantly less than those of the control group. Although phase I responses did not differ during comparisons among ketorolac tromethamine-administered groups, phase II responses decreased significantly in groups that received 150 and 400 microg of ketorolac tromethamine. Intrathecally administered ketorolac tromethamine reduced nociceptive responses and exhibited no untoward neurological effect even at large doses. However, its intrathecal use as a safe alternative drug for chronic pain remains to be investigated in other species. IMPLICATIONS: The present study is unique because it has demonstrated that chronic intrathecal administration of ketorolac tromethamine in rats, even at considerably large doses, showed a potent analgesic effect during the formalin test without exhibiting any neurotoxic side effect.

Comparison of meperidine plus midazolam and fentanyl plus midazolam in procedural sedation: a double-blind, randomized controlled trial.

This double-blind, randomized, prospective study was conducted to compare the analgesic and sedative efficacy of fentanyl and meperidine in orthopedic closed reduction of fractures and dislocations undertaken in the emergency department. Seventy consecutive adult patients with fractures or dislocations suitable for reduction were randomized to receive fentanyl (1 mcg/kg; n = 36) or meperidine (0.5 mg/kg; n = 34) in combination with midazolam (0.02 mg/kg). Vital signs and alertness scale scores of the patients were monitored. The Visual Analog Scale (VAS) was used to determine the degree of pain. There was no statistically significant difference between the VAS mean scores of the fentanyl and meperidine groups (t test, P = .772). The need for additional analgesic drugs was significantly more frequent in patients receiving meperidine (P = .018). No adverse events, such as hypotension or respiratory depression, were noted. Euphoria occurred in one patient in the fentanyl group. Although dose requirements differ, fentanyl and meperidine provide effective and reliable analgesia in closed reduction of fractures and dislocations.

Evaluation of physical findings in acute wrist trauma in the emergency department.

OBJECTIVE: The aim of the study was to evaluate the value of physical findings to predict fracture in patients with acute wrist trauma. METHODS: This prospective clinical study was conducted over a period of four months from December 1998. The patients who were older than 18 years and presenting with acute wrist trauma within 24 hours of the time of injury were included in the study. Magnetic resonance imaging (MRI) was done for the patients who had inconsistency between clinical and radiographic diagnosis. RESULTS: Fifty-five patients were included in the study. Four fractures were diagnosed on the MRI of eight patients who have contradiction between clinical diagnosis and X-ray studies. The positive predictive values of edema, localized tenderness, pain on active and passive motion, pain with grip and pain in supination were found as 95.2%, 67.3%, 77.3%, 91,7%, 89.3%, and 96%, respectively. Physical findings having high sensitivity were found as localized tenderness (94.3%), pain on the active and passive motion (97.1%, 94.3%, respectively). Pain on the active and passive motion were determined as physical findings with highest negative predictive values (%90.9, %89.5, respectively). CONCLUSION: Edema, pain on grip and supination, and especially pain on passive and active motion and localized tenderness can be valuable to predict or rule out fracture in acute wrist trauma cases who have no deformity.

Appropriateness of emergency department visits in a Turkish university hospital.

AIM: To determine the patterns and appropriateness of patients' use of a university hospital emergency department. METHODS: During a 14-day period in November 1998, we collected demographic and socio-economic data, reasons for preferring emergency department care, and patient visit data from consecutive patients visiting our tertiary-care university hospital emergency department. The principle investigator reviewed the study information forms and classified visits according to the classification of Afilalo into three categories: category I--emergent emergency department visits; category II--needing evaluation within 6 hours, either in emergency department or elsewhere; or category III--needing evaluation after more than 6 hours. Three emergency medicine residency-trained physicians determined the appropriateness of emergency department evaluation. Patients in the categories II and III were retrospectively reclassified as appropriate or inappropriate, according to availability of care at the outpatient facility at the hour of initial emergency department presentation. RESULTS: Complete data were collected from 1,155 (96.2%) of 1,201 patients visiting our emergency department during the study period. There were 69% (n=795) appropriate of visits. The mean stay at emergency department of inappropriate users lasted 66 min. The main reasons of inappropriate users to prefer emergency department care were its proximity, satisfaction with care, worsening symptoms, and unavailability of care in a regular clinic. CONCLUSION: Although inappropriate emergency department usage was high, these patients had relatively short emergency department stays. The impact on emergency department resource utilization and "over-crowding" by these patients may not be as great as commonly perceived.