Role Of Sedation Research Articles

Rapid analysis of neurotransmitters in rat brain using ultra‐fast liquid chromatography and tandem mass spectrometry: application to a comparative study in normal and insomnic rats

Neurotransmitters and their metabolites in central nervous system were known to play a significant role in sedation and hypnosis. A rapid and sensitive UFLC-MS/MS method for simultaneous determination of serotonin, 5-hydroxyindole acetic acid (5-HIAA), tryptophan (Try), dopamine (DA), norepinephrine (NE), γ-aminobutyric acid (GABA), glutamic acid (Glu) and acetylcholine (Ach) in rat brain without derivatization, ion-pairing reagent or pre-concentration was developed. Analytes and IS were separated on a Inertsil ODS-EP column (150 mm × 4.6 mm, 5 µm particles) and analyzed in a single chromatographic run in less than 9.0 min, using gradient elution with the mobile phase consisting of methanol and 0.01% acetic acid in water at a flow rate of 1.2 ml min(-1) . The detection of the analytes was performed on 4000Q UFLC-MS/MS system with turbo ion spray source in positive ion and multiple reaction monitoring mode. The developed method provided excellent linear calibration curves for the assay of analytes (R(2) ≥ 0.9915). Limits of quantification were in the range of 1.0 ng ml(-1) to 1.0 µg ml(-1) for the analytes in rat brain. Intra- and inter-day precision and accuracy of analytes were well within acceptance criteria (15%). Mean extraction recoveries of analytes and IS from rat brain were all more than 80.0%. Furthermore, the validated method was successfully applied to comparing profiles of analytes in normal and insomnic rat brains. Results indicated that there were statistically significant differences for serotonin, 5-HIAA, DA, NE, Glu and Ach, but no significant difference for Try and GABA between two groups.

Intensive care delirium: the new black

Intensive care delirium: the new black

The role of sedation on cataract surgery

Topikal anestezi, saydam kornea kesisinden yapilan fa- koemulsifikasyon katarakt cerrahisi icin genellikle yeterli ve etkin okuler anestezi saglamaktadir. Ancak asiri endiseli, kaygili ve kooperasyonu guc olan olgularda intraoperatif problemlerle karsilasma hic de azimsanmayacak kadar cok- tur. Bu olgularda uygulanan oral veya intravenoz sedasyon, bu problemleri buyuk oranda ortadan kaldirmaktadir. Bu derlemenin amaci, saydam kornea kesisinden yapilan fa- koemulsifikasyon katarakt cerrahisinde sedasyonun rolu ve olasi sedasyon alternatiflerinin degerlendirilmesidir. Topical anesthesia for clear corneal phacoemulsification cataract surgery usually provides adequate and effective ocular anesthesia. However, the possibility of intraoperative complications is not rare in anxious, distressed and uncoop- erative patients. In these cases, oral or intravenous sedation largely eliminates these problems. The purpose of this re- view is to evaluate the role of sedation in cataract surgery and possible sedation alternatives.

Psychomotor Agitation in Critically Ill Patients and the Role of Sedation

Critically ill patients often receive analgesia and sedation to keep them comfortable and to prevent agitation and delirium, which are serious, common and yet frequently underdiagnosed forms of brain dysfunction in intensive care environment with unclear but often unfavorable contribution to patient outcomes. Apart from delirium assessment and screening the most important aspect of ICU management is understanding the drugs given to patients and their specific advantages and disadvantages. It is crucial for clinicians and units to develop guidelines and protocols for the administration of sedatives depending on the type of patient population. Newer drugs, such as dexmedetomidine and remifentanyl, should be introduced and extensively studied. The immunomodulating effects of sedation also must be explored, as these properties may greatly affect outcome. With an increased understanding of sedative drugs will come an improved ability to use multiple drugs at specific times during the course of hospital treatment. Key words: delirium, sedation, analgesia.

Antiaggregatory effect of midazolam on human platelets during monitored anesthesia care for trans-vaginal oocyte retrieval

BackgroundMidazolam plays a major role in sedation and large doses might be used under certain circumstances. Trans-vaginal oocyte retrieval is one of the most painful procedures in which monitored anesthesia care (MAC) is needed. The mechanism by which midazolam exerts anti-aggregation of human platelets is still unclear.This work aimed to investigate the in vivo suppressing effect of midazolam on human platelet aggregation.MethodsSixty adult females ASA I–II, scheduled for trans-vaginal ultrasound oocyte retrieval by combined intravenous midazolam sedation with paracervical local nerve block were included. At the end of the procedure, it was found that the range of total midazolam consumption was 4.9–9 mg. Thereby, patients were divided into three groups according to the total consumption of midazolam: Group I (4.9–6.2 mg), Group II (6.3–7.6 mg), Group III (7.7–9 mg). Patients who needed other drugs for sedation were excluded. Pre- and post-operative Bleeding Time (BT) were recorded. Two blood samples were collected from each patient to test the inhibitory effect of midazolam on platelet aggregation. Platelet aggregation was tested using platelet-aggregometer. ELISA was used to measure thromboxane B2 formation. Flowcytometry was used to evaluate whether glycoprotein IIb–IIIa complex is the receptor site for the antiplatelet action of midazolam.ResultsOnly 51 patients completed the study: Group I (n = 16), Group II (n = 24), and Group III (n = 11). Bleeding Time (BT) showed significant prolongation in group III compared to basal levels. Midazolam suppressed platelet aggregation in a dose-dependent manner as detected by aggregometer. Glycoprotein IIb–IIIa complex is not its site of action as shown by flowcytometric analysis. Lastly, thromboxane B2 was significantly inhibited by midazolam.ConclusionThis study revealed that midazolam dose-dependently inhibits platelet aggregation by a mechanism not involving the binding of glycoprotein IIb–IIIa complex (fibrinogen receptor). It was also found that midazolam inhibits thromboxane A2 formation.

In vivo microdialysis with LC–MS for analysis of spinosin and its interaction with cyclosporin A in rat brain, blood and bile

Spinosin, a major bioactive herbal ingredient isolated from Semen Ziziphi Spinosae, plays an important role in sedation and hypnosis. However, the pharmacokinetic behavior of spinosin in special sites has not been reported. Microdialysis (MD) technique, as a continuous, realtime monitoring sampling technique, is very suitable for the evaluation of the disposition of diverse drugs. To obtain more useful information on spinosin, an in vivo microdialysis sampling technique with High Performance Liquid Chromatography–mass spectrograph (HPLC–MS) method was developed to investigate the pharmacokinetics of spinosin and its interaction with cyclosporin A (CsA) in the brain, blood and bile of rats. The method was validated in terms of selectivity, linearity and sensitivity, and showed advantages in monitoring the pharmacokinetic behavior of drugs. The results revealed that CsA has obvious effects on the pharmacokinetic process of spinosin. When co-administered, the area under the curve (AUC) of spinosin in blood, bile and brain increased from 205.70 to 673.51 mg min/L, 7.77 × 10 4 to 1.25 × 10 5 mg min/L, and 2.09 to 5.58 mg min/L, respectively. The t 1/2 values of spinosin in blood, bile and brain also changed from 48.07 to 95.04 min, from 97.20 to 152.21 and from 42.18 to 73.83 min, respectively. These results demonstrated that the CsA decreased the efflux of spinosin through the inhibition of P-glycoprotein (P-gp) efflux transporter and it might be used as a group of P-gp substrate. Other transporters or pathways may also be involved in the metabolism of spinosin.

Sedatives for opiate withdrawal in newborn infants

Neonatal abstinence syndrome (NAS) due to opiate withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties, weight loss and seizures. Treatments used to ameliorate symptoms and reduce morbidity include opiates, sedatives and non-pharmacological treatments. To assess the effectiveness and safety of using a sedative compared to a non-opiate control for NAS due to withdrawal from opiates, and to determine which type of sedative is most effective and safe. This update included searches of the Cochrane Central Register of Controlled Trials (Issue 1, 2010), MEDLINE 1966 to April 2010 and abstracts of conference proceedings. Trials enrolling infants with NAS born to mothers with an opiate dependence with > 80% follow-up and using random or quasi-random allocation to sedative or control. Control could include another sedative or non-pharmacological treatment. Each author assessed study quality and extracted data independently. Seven studies enrolling 385 patients were included. There were substantial methodological concerns for most studies including the use of quasi-random allocation methods and sizeable, largely unexplained differences in reported numbers allocated to each group.One study reported phenobarbitone compared to supportive care alone did not reduce treatment failure or time to regain birthweight, but resulted in a significant reduction in duration of supportive care (MD -162.1 min/day, 95% CI -249.2, -75.1). Comparing phenobarbitone to diazepam, meta-analysis of two studies found phenobarbitone resulted in a significant reduction in treatment failure (typical RR 0.39, 95% CI 0.24, 0.62). Comparing phenobarbitone with chlorpromazine, one study reported no significant difference in treatment failure.In infants treated with an opiate, one study reported addition of clonidine resulted in no significant difference in treatment failure, seizures or mortality. In infants treated with an opiate, one study reported addition of phenobarbitone significantly reduced the proportion of time infants had a high abstinence severity score, duration of hospitalisation and maximal daily dose of opiate. Infants with NAS due to opiate withdrawal should receive initial treatment with an opiate. Where a sedative is used, phenobarbitone should be used in preference to diazepam. In infants treated with an opiate, the addition of phenobarbitone or clonidine may reduce withdrawal severity. Further studies are needed to determine the role of sedatives in infants with NAS due to opiate withdrawal and the safety and efficacy of adding phenobarbitone or clonidine in infants treated with an opiate for NAS.

Posttraumatic stress disorder–related symptoms after critical care: The role of sedation and family

van Rijk, Maartje C. MD, PhD; Wittekamp, Bastiaan H. J. MD; Tjan, David H. T. MD; van Zanten, Arthur R. H. MD, PhD Author Information

Posttraumatic stress disorder–related symptoms after critical care: The role of sedation and family

Granja, Cristina MD, PhD; Amaro, Augusta MD; Gomes, Ernestina MD; Carneiro, Antonio MD; Ribeiro, Orquídea BSc; Costa-Pereira, Altamiro MD, PhD; Jones, Christina BSc, MPhil, PhD, PG Dip Psych Author Information

The Role of Sedation and Pulse Oximetry During Upper Gastrointestinal Endoscopy

To determine the changes in oxygen saturation, blood pressure and pulse rate during endoscopic procedure and to evaluate--oesophagogastroduodenoscopy (OGD) related discomfort assessed by the patient. It is observational case control study. Baseline pulse, blood pressure and oxygen saturation were monitored before procedure, at one minute of procedure, at five minute and soon after procedure. Patients were randomly selected according to lottery system (1: without sedation and 2: with sedation) and divided into two groups; without and with sedation. Before leaving department they were asked about level of discomfort during and after procedure. Patient's mean age +/- SD: 36.65, +/- 11.42 years and 53.3% were men. Base line mean oxygen saturation among sedated patient were 96.77 +/-1.56 % and 97.23, +/- 2.26 % respectively (P = 0.358). Mild to moderate hypoxia was noted more in sedated patient than in non sedated patient. Severe hypoxia was noted in 3.3% of sedated patient. No statistically significant change was noticed in pulse and blood pressure in both the group. None or only slight discomfort was experienced by 9.4% in non sedated group and 90.6% in sedated group. Severe discomfort by 96.4% in non sedated group and 3.6% in sedated group. There is slight more incidence of mild hypoxia in sedated group than in non sedated group but no change in pulse and blood pressure. However, sedated patient have significant less level of discomfort than in non sedated group. Though routine use of pulse oxymeter is not necessary, routine use of sedation during endoscopy is recommended.

Pharmacology Review

Advances in the understanding of neonatal pain have created interest in the use of medications during commonly performed procedures in the neonatal intensive care unit. A number of small studies have examined the role of sedatives, narcotics, miscellaneous anesthetics, and neuromuscular blockers in providing a more comfortable experience for the patient during nonemergent tracheal intubation. However, the most effective combination and doses of these medications is currently unknown. This review discusses the findings of selected studies that have been used to improve the intubating experience of patient and clinician.

Future Directions in Endoscopic Sedation

The role of sedation in endoscopic procedures has increased and so has the demand for advances in its administration. The pursuit of new agents or administration techniques and their study specific to endoscopic nonsurgical procedures is necessary to improve patient comfort and safety.The science of moderate and deep sedation specific to endoscopy is fledgling but approaching new horizons.

Delirium in cancer patients: a focus on treatment-induced psychopathology

Delirium is a neuropsychiatric syndrome that occurs frequently in cancer patients, especially in those with advanced disease. Recognition and effective management of delirium is particularly important in supportive and palliative care, especially in view of the projected increase in the elderly population and the consequent potential for the number of patients both diagnosed and living longer with cancer to increase substantively. Studies of delirium in a variety of settings have generated new insights into phenomenology, assessment tools, the psychomotor subtypes, potential patho-physiological markers, pathogenesis, reversibility, and the role of sedation in symptom control. Validated tools exist to assist in the assessment of delirium. Although our understanding of the pathogenesis of delirium has improved somewhat, there remains a compelling need to further elucidate the underlying pathophysiology, especially in relation to opioids and the other psychoactive medications that are used in supportive care. Further trials are needed, especially in patients with advanced disease to determine predictive models of reversibility, preventive strategies, outcomes, and to assess the role of antipsychotic and other medications in symptomatic management.

Neuromyopathies acquises en réanimation, délirium et sédation en réanimation

ICU-acquired neuromyopathy (NMAR) and delirium are the two most frequent and severe neurological complications of intensive care medicine. Their mechanisms still remain to be elucidated. The objective of this review is to address the potential role of sedation in occurrence of these complications. There is no evidence that sedation is involved in NMARs. However, the hypothesis that muscle inactivity induced by sedation fosters NMAR is an argument to discontinue or reduce sedatives infusion whenever possible. It is also recommended not to administer propofol more than 48 h at an infusion rate above 5 mg/kg per hour in patients with systemic inflammatory response syndrome, because of the risk of propofol infusion syndrome, which includes notably rhabdomyolysis. The relationship between delirium and sedation are controversial because in most studies, patients were considered delirious though being still sedated and multivariate analysis was lacking. One study showed that lorazepam given continuously was an independent risk factor for daily transition to delirium 24 h later with a 20% increase risk of every unit dose (expressed as log(e)mg). The impact of deepness, daily interruption or titration of sedation on the prevalence of delirium has never been assessed but it seems that deep sedation has to be avoided.

Role of sedation and analgesia in mechanical ventilation*

Keane HealthCare Solutions, Melville, NY (Carlon) Internal Medicine, Washington University School of Medicine, St. Louis, MO (Combs)

Role of sedation and analgesia in the pediatric intensive care unit

Role of sedation and analgesia in the pediatric intensive care unit

Agents for sedation in ophthalmic surgery: A review of the pharmacodynamics and clinical applications

Sedation is often required to improve patient comfort during the placement of local blocks in eye surgery. The ideal sedative should have a rapid onset of action and be able to ensure immobility while allowing for patients to respond to verbal commands. Furthermore, ideal sedatives should provide amnesia, have a sufficiently short duration of action to facilitate patient cooperation during surgery, have minimal side effects and allow for a rapid return to home-readiness. Combined analgesic and sedative regimes are widely used in tandem with local/regional blocks; however, potential problems with sedative/narcotic agents are considerable. These complications include ventilatory depression and loss of airway control with hypoxia and hypercapnia, and may cause the patient to become confused intra-operatively. The role of sedation in a wide variety of ophthalmic procedures as well as the variation in sedative agents used with regards to dosage regimes and drug combinations as applied in clinical practice can only be illustrated by referring to the published data. As a result, the goal of this paper is to examine the spectrum of sedative drugs that have been used in the process of eye surgery as published in the literature since 1990 with special attention being given to the pharmacodynamics and clinical applications of relevant drugs in current use. In conclusion there does not seem to be one drug or one regimen indicative of standardization of sedation practice in eye surgery. It rather seems as if there could be a competition between drugs and regimens for the position of the best and most favourable place in the armamentarium of sedationists and anaesthesiologists. There could be strong indications from the literature that drugs like midazolam, propofol,and remifentanil are the favourites for sedation in eye surgery. It might be necessary to take another look at the group of alpha-2 adrenergic agonists and also perhaps at low-dose ketamine.

Sedation during regional anesthesia: inhalation versus intravenous

Sedation of patients either with or without regional anesthesia is discussed to ascertain sedation requirements in the two groups. The differences between 'monitored anesthesia care' and conscious sedation are defined. Several current and promising methods with which we can evaluate a patient's degree or level of sedation are assessed. Also noted are safety concerns regarding monitoring solutions for patients undergoing monitored anesthesia care. Well established techniques, including some which are decidedly 'low tech', are examined. Several routes of intravenous administration are discussed along with patient variables. Sevoflurane sedation is mentioned with regards to administration, advantages and drawbacks. Several modalities have been studied for evaluation of a patient's level of sedation, some of which have little applicability in the operating room. Processed electroencephalographic monitoring has tremendous promise but is currently not reliable enough to assess sedation level. Sevoflurane has a role in sedation, providing the limitations are understood. One drawback of sevoflurane is its greater degree of disinhibition when compared with intravenous agents, necessitating conversion to general anesthesia. Evaluating the degree of patient sedation is a need that technology has yet to meet. Several techniques have been tried in intensive care units but have little utility in the operating room. Utilization of processed electroencephalogram waveforms has the greatest potential but is of limited value at the present time. Sevoflurane is demonstrated to have a limited role in sedation but may prove useful in specific circumstances.

Mervyn Maze, M.B., Ch.B., F.R.C.P.: recipient of the 2003 Excellence in Research Award.

Mervyn Maze, M.B., Ch.B., F.R.C.P.: recipient of the 2003 Excellence in Research Award.

Role of sedation in weaning children off ventilators

Role of sedation in weaning children off ventilators