Intravenous Administration Of Midazolam Research Articles

The association between midazolam premedication and postoperative delirium - a retrospective cohort study

Study objectiveTo evaluate the association between midazolam premedication and postoperative delirium in a large retrospective cohort of patients ≥70 years. DesignRetrospective cohort study. SettingA single tertiary academic medical center. PatientsPatients ≥70 years having elective non-cardiac surgery under general anesthesia from 2020 to 2021. InterventionsMidazolam premedication, defined as intravenous midazolam administration prior to induction of general anesthesia. MeasurementsThe primary outcome, postoperative delirium, was a collapsed composite outcome including at least one of the following: a positive 4A's test during post-anesthesia care unit stay and/or the initial 2 postoperative days; physician or nursing records reporting new-onset confusion as captured by the CHART-DEL instrument; or a positive 3D-CAM test. The association between midazolam premedication and postoperative delirium was assessed using multivariable logistic regression, adjusting for potential confounding variables. As secondary analysis, we investigated the association between midazolam premedication and a composite of other postoperative complications. Several sensitivity analyses were performed using similar regression models. Main resultsIn total, 1973 patients were analyzed (median age 75 years, 47% women, 50% ASA score ≥ 3, 32% high risk surgery). The overall incidence of postoperative delirium was 15.3% (302/1973). Midazolam premedication was administered to 782 (40%) patients (median [IQR] dose 2 [1,2] mg). After adjustment for potential confounding variables, midazolam premedication was not associated with increased odds of postoperative delirium, with adjusted odds ratio of 1.09 (95% confidence interval 0.82–1.45; P = 0.538). Midazolam premedication was also not associated with the composite of other postoperative complications. Furthermore, no association was found between midazolam premedication and postoperative delirium in any of the sensitivity analyses preformed. ConclusionsOur results suggest that low doses of midazolam can be safely used to pre-medicate elective surgical patients 70 years or older before non-cardiac surgery, without significant effect on the risk of developing postoperative delirium.

General anesthesia in spontaneous respiration with intravenous ketamine in patients undergoing pulsed-field ablation

Abstract Funding Acknowledgements Type of funding sources: None. Background Thermal ablation of atrial fibrillation (AF) by means of radiofrequency or cryo-balloon is usually performed under general anesthesia, deep sedation, or conscious sedation at operator’s discretion and based on the general condition of the patient. However, a standardized sedation protocol when performing a non-thermal ablation, such as pulsed-field ablation (PFA) through irreversible cellular electroporation, has not been well established. Purpose We report our preliminary experience of a general anesthesia in spontaneous respiration protocol with ketamine used at a high-volume center during ablation of AF with a new PFA system. Methods All consecutive patients (pts) undergoing AF ablation with PFA at our center were included. Our sedation protocol consists of intravenous administration of midazolam (1+1 mg), fentanyl (25+25+25+25 mcg/kg) at low doses before local anesthesia with lidocaine (200mg) administration. Patients underwent sedation under spontaneous respiration by administering oxygen (4-6 l/min) through a face mask with nasal cannula. Local anesthesia was performed before the percutaneous femoral venous access. Soon after the trans-septal puncture, heparin (1 mg/kg) and atropine (1 mg, to mitigate anticipated bradycardia) were injected, followed by a second bolus of midazolam (1 mg). Ketamine adjunct (1 mg/kg) was then injected about 5 minutes before the first PFA delivery which was titrated to effect based on patient’s condition, response and changes in vital signs (total ketamine adjunction of 2 mg/kg). For quantitative assessment the Numeric Rating Scale for Pain (NRS) was applied. For qualitative assessment a 3-levels satisfaction evaluation was retrieved. The ablation endpoint was PVI as assessed by entrance and exit block. Results Forty-two pts were included in this analysis (mean age of 66±9 years,72% were male, CHA2DS2VASc score=2 [IQR 1–3], median body mass index 24[20-48]kg/m2, 35% had respiratory diseases – e.g. asthma, OSAS, COPD –). At baseline, before sedation, mean systolic blood pressure was 140.5+20.1mmHg and mean oxygen saturation was 97.9+2.1%. PVI was achieved in all the patients. The number of PFA applications to reach PVI was 33.4+3 (time to PVI = 25+4min). In two cases additional PFA lesion sets were deployed outside the PVs. Lab occupancy time was 122±32min, skin-to-skin time was 78±35min and fluoroscopy time was 23±14min. All the patients achieved a NRS ≤ 3. Satisfaction level was found to be acceptable in all procedures by both the patient and the primary operator (Score equal to 0). No major procedure-related adverse events were reported. Conclusion The PFA procedure has a short execution time. The standardized anesthetic protocol with the administration of drugs with rapid onset and pharmacological offset at low doses was effective and safe with an optimal degree of patient and operator satisfaction.

Does Routine Sedation Influence Anxiety and CRP levels in Patients Undergoing Elective Coronary Catheterization?

Cardiac catheterization is associated with patient anxiety. Benzodiazepines are often used to relieve anxiety in this setting. The association between anxiety level and C-reactive protein (CRP) remains equivocal. We sought to determine whether anxiety and CRP levels in patients undergoing elective left heart catheterization differ when routine sedation with midazolam is administered. Patients undergoing elective left heart catheterization were randomly assigned to receive 2 mg of midazolam intravenously or placebo before access insertion in a double-blinded manner. Levels of anxiety were assessed using the State-Trait Anxiety Inventory for Adults (short form) and high-sensitivity CRP at the time of admission and discharge. Surrogate markers for anxiety, such as blood pressure and pulse, were recorded before and after the procedure. Patient-perceived discomfort was measured with a visual analog scale (VAS) on a 0-10 scale. One hundred patients (52 receiving treatment, 48 receiving placebo) participated in the study. Baseline demographic characteristics and previous medical conditions were well balanced between groups. Anxiety level, systolic blood pressure, and diastolic blood pressure were all higher at procedure start than post procedure, but did not differ between the groups. CRP levels were similar at both time points for patients in both groups (0.77 ± 2.53 mg/L pre procedure and 0.70 ± 2.08 mg/L post procedure in the midazolam group vs 0.79 ± 1.39 mg/L pre procedure and 0.83 ± 1.45 mg/L post procedure in the placebo group). Discomfort level assessment was also alike (2.6 ± 2.4 in the treatment group vs 3.4 ± 2.5 in the placebo group; P=.12). Intravenous midazolam administration does not seem to relieve patient discomfort and anxiety nor does it influence CRP level. Therefore, an approach tailored to the patient is advisable.

Safety and effectiveness of deep sedation in pediatric patients undergoing flexible fibroscopy in spontaneous breathing

Invasive diagnostics and minor surgical procedures with deep sedation on pediatric patients, such as fibroscopic examination, have increased over the past decade. The aim of this study was to evaluate the usefulness and safety of an anesthesiological technique, based on the use of midazolam and ketamine, conducted in spontaneous breathing on a population of pediatric patients with suspected tracheobronchial pathologies. Pediatric patients from birth to 18 years old who underwent sedation diagnostic fibroscopy between April 2018 and March 2019, were enrolled. The anesthesiological technique provided was the intravenous administration of midazolam 0.2 mg/kg and ketamine 2 mg/kg in spontaneous breathing using a face mask with support of O2 and air. Vital signs such as Heart rate (HR), Systolic and Diastolic blood pressure (PAS and PAD) and Arterial oxygen saturation were recorded at the beginning of the procedure, 10 minutes and 30 minutes from the start. Other parameter evaluated were patient’s level of consciousness, quality of the procedure, major and minor complications, adequate recovery of the waking state. Sixteen patients were enrolled, 12 males and 4 females aged between 2 days of life and 7 years. Laryngomalacia tracheomalacia, tracheoesophageal fistula, and congenital airway malformations were the most frequent diseases. As for vital signs: the HR has gone from an average value of 133.4 ± 16.26 bpm at T0 to an average value of 129.3 ± 16.55 bpm at T10 and 133.7 ± 17.35 bpm at T30; PAS and PAD had not significant variations. Among drugs available for the fibroscopic examinations, the combined use of intravenous midazolam 0.2 mg/kg and ketamine 2 mg/kg is safe and well tolerated, reducing the anxiety associated with the examination, without major complications. The current literature is lacking in studies that have included such small and low weight patients. It would be interesting to make a comparison between various sedation techniques in order to identify the safest for the pediatric population.

A comparison of intravenous midazolam and diazepam in management of status epilepticus in children.

To compare the efficacy of intravenous midazolam and diazepam in the management of status epilepticus seizures in children. The comparative study was conducted in the paediatric neurological emergency unit of The Children's Hospital and the Institute of Child Health, Multan, Pakistan, from December 15, 2018, to May 14, 2019, and comprised paediatric patients of status epilepticus seizures which were divided into Diazepam and Midazolam groups. Data was analysed using Graph-Pad Prism 5. Of the 164 patients, 82(50%) were in each of the two groups. There was no significant difference between the groups in terms of weight, age, residence area of patients and mean duration of seizures (p>0.05). Status epilepticus seizures subsided after intravenous midazolam administration in 77(93.90%) cases, while success in the diazepam group 64(78.05%) (p<0.05). Mean time taken by midazolam to halt seizures was significantly shorter than diazepam (p<0.05) and less cases of treatment failure were observed with intravenous midazolam (p<0.05). Somnolence was observed after diazepam administration in 47(57.3%) cases (p=0.0001). Intravenous midazolam was found to be superior in efficacy than intravenous diazepam in controlling status epilepticus seizures.

Postoperative expressive aphasia associated with intravenous midazolam administration: a 5-year retrospective case-control study.

ObjectivesThis study aimed to investigate the epidemiology of intravenous midazolam-induced postoperative expressive aphasia (EA).MethodsThe incidence rate, risk ratio, and contributing factors to intravenous midazolam-induced postoperative EA were analyzed retrospectively in 6756 orthopedic patients. A telephone interview was conducted with patients with EA after surgery.ResultsPatients were allocated to either the midazolam group (n = 6178) or no-midazolam group (n = 578). Twelve patients developed EA in the midazolam group, with an incidence of 0.19%, and no patient developed EA in the no-midazolam group. The mean age of EA patients was 70 years, and 92% were women. Among them, 75% received general anesthesia, and the mean dose of midazolam was 1.8 mg. EA was reversed in nine of 12 (75%) patients within 4 minutes of flumazenil administration, and >60 minutes were required to reverse EA in the other three patients (25%).ConclusionIntravenous midazolam administration for preoperative sedation caused transient EA in 0.19% of patients, especially elderly women who received general anesthesia, and EA could be reversed by flumazenil.

Regulatory effects of propofol on high-dose remifentanil-induced hyperalgesia.

We aimed to evaluate the regulatory effects of propofol on high-dose remifentanil-induced hyperalgesia. A total of 180 patients receiving laparoscopic cholecystectomy were randomly divided into sevoflurane + high-dose remifentanil (SH) group, sevoflurane + low-dose remifentanil (SL) group and propofol + high-dose remifentanil group (PH) group (n=60). After intravenous administration of midazolam, SH and SL groups were induced with sevoflurane and remifentanil, and PH group was induced with propofol and remifentanil. During anesthesia maintenance, SH and SL groups were given 0.3 microg/kg/min and 0.1 microg/kg/min sevoflurane and remifentanil respectively, and PH group was given 0.3 microg/kg/min propofol and remifentanil. The three groups had significantly different awakening time, extubation time and total dose of remifentanil (P<0.001). Compared with SL group, periumbilical mechanical pain thresholds 6 h and 24 h after surgery significantly decreased in SH group (P<0.05), and the visual analog scale (VAS) scores significantly increased 30 min, 2 h and 6 h after surgery (P<0.05). Compared with SH group, periumbilical mechanical thresholds 6 h and 24 h after surgery were significantly higher in PH group (P<0.05), and VAS scores 30 min, 2 h and 6 h after surgery were significantly lower (P<0.05). PH group first used patient-controlled intravenous analgesia pump significantly later than SL group did (P<0.05). The total consumptions of sufentanil in PH and SL groups were significantly lower than that of SH group (P<0.05). The incidence rates of bradycardia and postoperative chill in PH and SH groups were significantly higher than those of SL group (P<0.05). Anesthesia by infusion of high-dose remifentanil plus sevoflurane caused postoperative hyperalgesia which was relieved through intravenous anesthesia with propofol.

Prevention of Cognitive Dysfunction after Cataract Surgery with Intravenous Administration of Midazolam and Dexmedetomidine in Elderly Patients Undergoing Cataract Surgery.

Background:This study aimed to compare the effects of preoperative administration of midazolam and dexmedetomidine on cognitive dysfunction prevention after cataract surgery.Materials and Methods:This research was a double-blind controlled clinical trial. In this study, 150 candidates for cataract surgery under general anesthesia, over 65 years, and similar to American Society of Anesthesiologists I and II characteristics were selected as the sample and randomly assigned to three groups. Participants of these three groups were treated with 0.1 mg/kg of midazolam, 1 μg/kg of dexmedetomidine, and the same volume of normal saline (control), respectively. Hemodynamic parameters and cognitive dysfunction score of the participants were measured using the Mini-Mental State Examination (MMSE) before the surgery, 24 h and 1 week after the surgery.Results:An evaluation of hemodynamic parameters before anesthesia up to 24 h after the surgery showed no significant difference between the midazolam, dexmedetomidine, and control groups in terms of systolic and diastolic blood pressure, heart rate, and blood oxygen saturation (P > 0.05). In addition, there was no statistically significant difference between the midazolam and dexmedetomidine groups in the MMSE score before the surgery and 24 h and 1 week after that (P > 0.05). However, there was a significant difference between these two groups and control (P < 0.05).Conclusion:There was no significant difference between midazolam and dexmedetomidine in reducing postoperative cognitive dysfunction (POCD). However, there is a significant difference between these two groups and control. Hence, either midazolam or dexmedetomidine can be prescribed to reduce POCD in cataract surgeries.

P1.03-044 EUS-Guided Sampling of Mediastinal Lymph Nodes and Abdominal Lesions in Lung Cancer

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS–TBNA) was introduced to provide access to mediastinal and hilar lymph nodes. However, it is difficult to use EBUS to approach the aortopulmonary window and paraesophagaeal stations. Transesophageal endoscopic ultrasound (EUS) was introduced to provide access to this area. In addition, transgastroduodenal endoscopic ultrasound can evaluate abdominal lesions. Endoscopic ultrasound fine needle aspiration (EUS-FNA) was performed under conscious sedation with the administration of intravenous midazolam and pethidine hydrochloride. It was performed with a convex array echoendoscope connected to an ultrasound scanning system. Lymph nodes of paraesophageal, subcarinal, lower paratracheal, subaortic, and upper paratracheal regions were evaluated from esophagus. Left adrenal gland and right adrenal gland were evaluated from stomach and duodenum, respectively. Abdominal lesions were also evaluated from stomach and duodenum. After obtaining tissue via EUS-FNA, the tissue was reviewed immediately (rapid on-site cytopathological evaluation: ROSE) by a cytopathologist. Subsequent punctures in the same patient were not performed before confirming the results of ROSE so as to minimize the complications. As to the lymph node level, the lower mediastinum and the aortopulmonary window are particularly important for detection by transesophageal EUS, whereas pretracheal and hilar lymph nodes are out of reach because of the interposition of air from the trachea and bronchi. EUS was chosen to assess the posterior mediastinum nodes (#5, 7, 8, or 9) but not the anterior ones. A final diagnosis was obtained by EUS-FNA in 76 patients. The lesions sampled were mediastinal lymph nodes (n=64; #5, 7, 8, or 9), abdominal lymph nodes (n=8), and adrenal gland (n=4). Repeat tumor biopsies from patients with acquired resistance were initially obtained through research efforts to ascertain mechanisms of resistance, but are now recommended to help select second-line therapies. However, such biopsies are associated with both risk and discomfort and may not always supply enough tumor tissue for genetic analyses. Although EUS–FNA does not provide access to pretracheal and hilar lymph nodes, EUS-FNA is an accurate, safe, and minimally invasive modality for evaluating mediastinal lymphadenopathy and abdominal lesions in patients suspected of having lung metastases.

R08 - Occasional sedation in the management of cancer pain

Background: Palliative sedation is an intentional reduction of the patient's awareness until the lost consciousness. It is used at the end of life to relieve severe and refractory symptoms in patients with advance stage of disease. Occasional sedation (OS) is not consider a type of palliative sedation. It reduces the patient's consciousness for a brief period and provides the patient awakining by discontinuing sedative medications. It can be used for invasive nursing actions or to give rest in patient with anxiety or insomnia. A very few licterature data exist for the use of OS in the management of cancer pain at the end of life. Material (patients) and methods: A retrospective analysis of patients with advanced cancer admitted to hospice from April 2015 to April 2106 was performed. The OS was proposed to patients with severe pain due to a particular trigger event when the use of opioids was not sufficient to control pain. Informations about epidemiologic and clinical characteristics, indications, duration, drugs, and outcomes was collected. Results: 266 patients entered the Hospice consecutively during the year. OS was offered to 6 cases with patient's consent. All of them received high doses of opioids for background pain. Indications for OS were: pain control during every dressing of large neoplastic lesions (n= 2) or pressure sores (n = 1), pain control during painful nursing cares (n = 2), pain and anxiey control every night (n= 1).The OS was carried out in all cases through intravenous administration of Midazolam (dose range 5 mg - 70 mg ) and Morphine. Duration of OS depended on desiderated time of awaking (range 1 hour -12 hours). In 2 of the 6 cases Flumazenil (0,1 mg i.v.) was used to awaken the patient with immediate effect. Conclusions: Pain can have high physical and emotional impact in the patient with advanced cancer. If opioids are not sufficient to control pain due to trigger events, OS can be considered. The OS is useful in complex dressings, painful nursing care practices and to control pain and anxiety overnight. The use of Flumazenil should always be considered to awaken the patient when the triggering pain is over.

Tourniquet-induced ischaemia-reperfusion injury: the comparison of antioxidative effects of small-dose propofol and ketamine

ObjectivesThe aim of the present study was to investigate the preventive effects of propofol and ketamine as small dose sedation during spinal anaesthesia on tourniquet-induced ischaemia-reperfusion injury. Methods30 patients were randomly assigned into two groups of 15 patients. In the propofol group, sedation was performed with propofol 0.2mg·kg−1 followed by infusion at a rate of 2mg·kg−1·h−1. In the ketamine group, a continuous infusion of ketamine 0.5mg·kg−1·h−1 was used until the end of surgery. Intravenous administration of midazolam was not used in any patients. Ramsay sedation scale was used for assessing the sedation level. Venous blood samples were obtained before propofol and ketamine infusion (T1), at 30minutes (min) of tourniquet ischaemia (T2), and 5min after tourniquet deflation (T3) for malondialdehyde (MDA) measurements. ResultsNo differences were noted between the groups in haemodynamic (p>0.05) and demographic data (p>0.05). There was no statistically significant difference between the two groups in terms of T1, T2 and T3 periods (p>0.05). There was a statistically increase observed in MDA values respectively both in Group P and Group K between the reperfusion period (1.95±0.59, 2.31±0.48) and pre-ischaemia (1.41±0.38, 1.54±0.45), and ischaemia (1.76±0.70, 1.71±0.38) (μmoL−1) periods (p<0.05). ConclusionsSmall-dose propofol and ketamine has similar potential to reduce the oxidative stress caused by tourniquet-induced ischaemia-reperfusion injury in patients undergoing arthroscopic knee surgery under spinal anaesthesia.

Effect of carbamazepine or phenytoin therapy on blood level of intravenously administered midazolam: a prospective cohort study.

Dental treatment of intellectually disabled patients is frequently performed under general anesthesia or sedation. Many of these patients have epilepsy and are medicated with antiepileptic drugs (AEDs). Carbamazepine (CBZ) and phenytoin (PHT) are known to promote the metabolism of midazolam, and the blood levels of midazolam in patients medicated with CBZ or PHT may be different from those in healthy individuals. In this study, we clarified the influences of CBZ and PHT on the blood level of intravenously administered midazolam in patients medicated with CBZ or PHT. The subjects were divided into the following groups: not medicated with AEDs (control group), medicated with only CBZ or PHT (mono CBZ/PHT group), and medicated with CBZ or PHT or both and other AEDs (poly CBZ/PHT group). General anesthesia was achieved using midazolam, propofol, and remifentanil, and then the blood midazolam level was measured at 10, 30, and 60min after intravenous midazolam administration. According to the results, the blood midazolam level was significantly lower in the mono and poly CBZ/PHT groups than in the control group. This finding suggests that intravenously administered midazolam may have a weaker effect in patients medicated with CBZ or PHT.

Effect of midazolam on memory during fiberoptic gastroscopy under conscious sedation.

As the fiberoptic gastroscopy using midazolam is being in widespread use, the exact nature of midazolam on memory should be clarified. We intended to examine whether midazolam causes selective anterograde amnesia and what impact it has on other aspects of memory and general cognitive function. We recruited healthy subjects undergoing fiberoptic gastroscopy under conscious sedation. At baseline, history taking for retrograde amnesia and the Korean version of the Montreal Cognitive Assessment were performed. A man's name and address were given immediately after intravenous midazolam administration. After gastroscopy, the subjects were asked to recall those items. By the time they had fully recovered consciousness, the same test was repeated along with the Korean version of the Montreal Cognitive Assessment and a test for retrograde amnesia. A total of 30 subjects were enrolled in this study. Subjects with high-dose midazolam showed lower scores in the immediate and delayed recall of "a man's name and address" compared with those with low-dose midazolam. The midazolam dose was inversely correlated with the delayed recall scores of "a man's name and address." On full recovery of consciousness, the subjects did not exhibit any of anterograde or retrograde amnesia. These findings suggest that midazolam causes transient selective anterograde amnesia in a dose-dependent manner.

Comparison of the Effects of 0.03 and 0.05 mg/kg Midazolam With Placebo on Prevention of Emergence Agitation in Children Having Strabismus Surgery

Background Midazolam has been widely studied for preventing emergence agitation. The authors previously reported that in children with sevoflurane anesthesia, intravenous administration of midazolam (0.05 mg/kg) before the end of surgery reduced the incidence of emergence agitation but prolonged the emergence time. This study was designed to test the hypothesis that a lower midazolam dose could suppress emergence agitation with minimal disturbance of the emergence time in children with sevoflurane anesthesia. Methods In this randomized, double-blind, placebo-controlled trial, 90 children (1 to 13 yr of age) having strabismus surgery were randomized to 1:1:1 to receive 0.03 mg/kg of midazolam, 0.05 mg/kg of midazolam, or saline just before the end of surgery. The primary outcome, the incidence of emergence agitation, was evaluated by using the pediatric anesthesia emergence delirium scale and the four-point agitation scale. The secondary outcome was time to emergence, defined as the time from sevoflurane discontinuation to the time to extubation. Results The incidence of emergence agitation was lower in patients given 0.03 mg/kg of midazolam (5 of 30, 16.7%) and patients given 0.05 mg/kg of midazolam (5 of 30, 16.7%) compared with that in patients given saline (13/of 30, 43.3%; P = 0.036 each). The emergence time was longer in patients given 0.05 mg/kg of midazolam (17.1 ± 3.4 min, mean ± SD) compared with that in patients given 0.03 mg/kg of midazolam (14.1 ± 3.6 min; P = 0.0009) or saline (12.8 ± 4.1 min; P = 0.0003). Conclusion Intravenous administration of 0.03 mg/kg of midazolam just before the end of surgery reduces emergence agitation without delaying the emergence time in children having strabismus surgery with sevoflurane anesthesia.

Thoracic spinal cord stimulation for low back pain in a patient with permanent pacemaker.

Sir, Spinal cord stimulation (SCS) for chronic pain management involves placement of epidural electrodes, which could theoretically evoke device-to-device interference in patients with a permanent cardiac pacemaker (PPM).[1] We report a case of a 52-year-old female patient with double-chamber Medronic Kappa KDR903® device with sensor accelerator-DDDR (Medtronic Inc., Minneapolis, MN, USA/compatible with bipolar diathermy) due to complete heart block, who underwent SCS implantation for treatment of severe chronic low back pain. Several oral analgesic regimens, non-invasive (hydro/physiotherapy) or minimal invasive (electro- acupuncture (EA)) treatment methods had been tested previously unsuccessfully or with extremely short duration of pain relief (24–36 h pain-free period after EA). Therefore, after consultation with a cardiologist, due to patient's history, she was deemed to be a good candidate for SCS. SCS implantation was carried out in the operating theatre under monitored anaesthesia care (MAC) with the patient in the prone position. Standard intraoperative monitoring included continuous electrocardiograph, intermittent non-invasive blood pressure monitoring (every 5 min), capnometry trend (CO2 sensor was attached inside the oxygen mask), and pulse oximetry. MAC was achieved by intermittent intravenous midazolam administration (0.05–0.1 mg/kg). An electrode lead was inserted with its tip at T9 level under real-time X-ray guidance (C-arm fluoroscopy unit). Correct electrode positioning produced paraesthesiae in low back during intraoperative test stimulation corresponding to patient's pain location. Initially, SCS device was programmed at a pulse rate of 80 Hz, a pulse width of 210 μs and an output voltage of 1.2 mV. Pacemaker sensitivity and possible device interference were tested in detail by a Medtronic technician perioperatively. During the trial period, SCS output voltage was increased to the maximum level tolerated by the patient to reveal any possible interference; and no interference was noted. After that, SCS was reset to the clinically chosen parameters mentioned before. Moreover, SCS amplitude was programmed to prevent possible overstepping of the tested safe upper energy level. After 2 days, permanent SCS implantation ensued following the above-mentioned safety measures. After 1 week, an X-ray revealed that the electrode tip had slipped from level T9 to T11. Therefore, SCS was reprogrammed to produce paraesthesiae in patient's pain location at a higher pulse width of 330 μs, whereas the rate and output voltage remained (80 Hz/1.2 mV). Re-interrogation of the pacemaker continued to reveal no interference. One week later, the patient was discharged and SCS device could be switched on and off and the energy level could be increased and decreased by the patient (within preset safe limits). Post-implantation follow-up (at 3–6–12 months) revealed significant pain relief, improvement of basic movement's performance and quality of life as these were documented according to appropriate scales used. This is a report of a safe and effective SCS implantation in a patient with PPM. Despite the theoretical risk of device-to-device interference in such a setting, there are several literature studies describing cases without any interference.[234] The only report of PPM-SCS interference was a case where both devices were used in the unipolar mode and PPM function was inhibited when SCS stimulation amplitude exceeded 1.9–2 mV.[4] Other literature reports of inter-device interference describe cases of simultaneous use of implantable cardioverter defibrillators (ICDs) and SCS, and due to the different behaviour of ICDs compared to PPMs they are not discussed further.[45] According to relevant literature, it seems that there are minimal chances of inter-device interference when both devices use bipolar mode.[2] Despite the fact that in our case, SCS and PPM were used simultaneously with safety and effectiveness, individual testing under careful monitoring is mandatory. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Comparison of the Effects of 0.03 and 0.05 mg/kg Midazolam with Placebo on Prevention of Emergence Agitation in Children Having Strabismus Surgery

Midazolam has been widely studied for preventing emergence agitation. The authors previously reported that in children with sevoflurane anesthesia, intravenous administration of midazolam (0.05 mg/kg) before the end of surgery reduced the incidence of emergence agitation but prolonged the emergence time. This study was designed to test the hypothesis that a lower midazolam dose could suppress emergence agitation with minimal disturbance of the emergence time in children with sevoflurane anesthesia. In this randomized, double-blind, placebo-controlled trial, 90 children (1 to 13 yr of age) having strabismus surgery were randomized to 1:1:1 to receive 0.03 mg/kg of midazolam, 0.05 mg/kg of midazolam, or saline just before the end of surgery. The primary outcome, the incidence of emergence agitation, was evaluated by using the pediatric anesthesia emergence delirium scale and the four-point agitation scale. The secondary outcome was time to emergence, defined as the time from sevoflurane discontinuation to the time to extubation. The incidence of emergence agitation was lower in patients given 0.03 mg/kg of midazolam (5 of 30, 16.7%) and patients given 0.05 mg/kg of midazolam (5 of 30, 16.7%) compared with that in patients given saline (13/of 30, 43.3%; P = 0.036 each). The emergence time was longer in patients given 0.05 mg/kg of midazolam (17.1 ± 3.4 min, mean ± SD) compared with that in patients given 0.03 mg/kg of midazolam (14.1 ± 3.6 min; P = 0.0009) or saline (12.8 ± 4.1 min; P = 0.0003). Intravenous administration of 0.03 mg/kg of midazolam just before the end of surgery reduces emergence agitation without delaying the emergence time in children having strabismus surgery with sevoflurane anesthesia.

Glycyrrhizin accelerates the metabolism of triptolide through induction of CYP3A in rats

Ethnopharmacological relevanceTriptolide (TP), a major active component of Tripterygium wilfordii, possesses various pharmacological activities with narrow therapeutic window and severe toxicities. Glycyrrhizin (GL), the principal bioactive ingredient of licorice root extract, has been reported to be concomitantly administered with TP in treatment of rheumatoid arthritis with the aim of potentiated efficacy and reduced toxicity. The aim of the study is to investigate the effect of GL on the pharmacokinetic profiles of TP and related mechanisms. Materials and methodsMale and female Wistar rats were randomly divided into two groups: Control group and GL group (pretreated with GL at 100mg/kg/day for seven consecutive days). After oral administration of TP at a single dose of 450μg/kg, plasma concentrations of TP were determined using HPLC–MS/MS and pharmacokinetic parameters were calculated by non-compartmental analysis using Phoenix WinNonlin 6.3 software. Since CYP3A is the primary isoform of cytochrome P450s responsible for the metabolism of TP, we further determined to what extent ketoconazole (KCZ), a potent CYP3A inhibitor, could influence the effect of GL on the pharmacokinetics of TP by comparing the pharmacokinetic profiles of TP in GL group (pretreated with GL) and GL+KCZ group (pretreated with both GL and KCZ), as well as verified whether pretreatment of GL could induce the activity of hepatic CYP3A by comparing the AUC parameters after intravenous administration of midazolam (MDZ), a typical probe drug for CYP3A, in rats pretreated with vehicle or GL. ResultsOur study revealed marked differences in pharmacokinetic profiling patterns of TP between male and female rats in the Control group; the plasma level of TP in males was far lower than that in females. After pretreatment with GL, the pharmacokinetic profiles of TP were significantly altered in both male and female rats; a remarkable decrease was found in the value of AUC∞, MRT∞ and t1/2 in the GL group, compared with the Control group. But such a decrease was reversed by KCZ; compared with the GL group, the values of AUC∞, MRT∞ and t1/2 were significantly increased in the GL+KCZ group. Pretreatment with GL notably increased the AUC∞ of 1׳-hydroxymidazolam (OH-MDZ) and the ratio of AUC∞ of OH-MDZ to MDZ, demonstrating induction of the activity of CYP3A by GL. ConclusionPretreatment with GL significantly accelerates the metabolic elimination of TP from the body mainly through induction of hepatic CYP3A activity. These results may help explain why toxicity of TP may be attenuated with concomitant use of GL.

Transcutaneous aortic valve replacement with the Edwards SAPIEN XT and Medtronic CoreValve prosthesis under fluoroscopic guidance and local anaesthesia only

ObjectiveTo assess the feasibility of transcatheter aortic valve implantation (TAVI; Medtronic CoreValve and Edwards SAPIEN XT) under local anaesthesia with only mild analgesic medication and fluoroscopic guidance.Methods461 patients underwent TAVI...

Analgesia e sedação durante a instalação do cateter central de inserção periférica em neonatos

Objetivou-se caracterizar as estratégias de analgesia e sedação em neonatos submetidos à instalação do cateter central de inserção periférica (CCIP) e relacioná-las ao número de punções venosas, duração do procedimento e posicionamento da ponta do cateter. Estudo transversal com coleta prospectiva de dados, realizado em uma unidade de cuidados intensivos neonatais de um hospital privado na cidade de São Paulo, no período de 31 de agosto de 2010 a 01 de julho de 2011, em que foram avaliadas 254 inserções do CCIP. A adoção de estratégias analgésicas ou sedativas ocorreu em 88 (34,6%) instalações do cateter e não esteve relacionada ao número de punções venosas, duração do procedimento ou posicionamento da ponta do cateter. As estratégias mais frequentes foram a administração endovenosa de midazolam em 47 (18,5%) e fentanil em 19 (7,3%) inserções do cateter. Recomenda-se maior adoção de estratégias analgésicas antes, durante e após o procedimento.

A Novel Maturation Function for Clearance of the Cytochrome P450 3A Substrate Midazolam from Preterm Neonates to Adults

Major changes in cytochrome P450 (CYP) 3A activity may be expected in the first few months of life with, later, relatively limited changes. In this analysis we studied the maturation of in vivo CYP3A-mediated clearance of midazolam, as model drug, from preterm neonates of 26weeks gestational age (GA) to adults. Pharmacokinetic data after intravenous administration of midazolam were obtained from six previously reported studies. Subjects were premature neonates (n=24; GA 26-33.5weeks, postnatal age (PNA) 3-11days, and n=24; GA 26-37weeks, PNA 0-1days), 23 children after elective major craniofacial surgery (age 3-23months), 18 pediatric intensive-care patients (age 2days-17years), 18 pediatric oncology patients (age 3-16years), and 20 healthy male adults (age 20-31years). Population pharmacokinetic modeling with systematic covariate analysis was performed by use of NONMEM v6.2. Across the entire lifespan from premature neonates to adults, bodyweight was a significant covariate for midazolam clearance. The effect of bodyweight was best described by use of an allometric equation with an exponent changing with bodyweight in an exponential manner from 0.84 for preterm neonates (0.77kg) to 0.44 for adults (89kg), showing that the most rapid maturation occurs during the youngest age range. An in-vivo maturation function for midazolam clearance from premature neonates to adults has been developed. This function can be used to derive evidence-based doses for children, and to simulate exposure to midazolam and possibly other CYP3A substrates across the pediatric age range in population pharmacokinetic models or physiologically based pharmacokinetic models.