Acute lung injury (ALI) is a devastating condition that places a heavy burden on public health resources. Although the need for effective ALI prevention strategies is increasingly recognised, no effective preventative strategies exist. The Lung Injury Prevention Study with Aspirin (LIPS-A) aims to test whether aspirin (ASA) could prevent and/or mitigate the development of ALI.
Methods and analysis
LIPS-A is a multicentre, double-blind, randomised clinical trial testing the hypothesis that the early administration of ASA will result in a reduced incidence of ALI in adult patients at high risk. This investigation will enrol 400 study participants from 14 hospitals across the USA. Conditional logistic regression will be used to test the primary hypothesis that early ASA administration will decrease the incidence of ALI.
Ethics and dissemination
Safety oversight will be under the direction of an independent Data and Safety Monitoring Board (DSMB). Approval of the protocol was obtained from the DSMB prior to enrolling the first study participant. Approval of both the protocol and informed consent documents were also obtained from the institutional review board of each participating institution prior to enrolling study participants at the respective site. In addition to providing important clinical and mechanistic information, this investigation will inform the scientific merit and feasibility of a phase III trial on ASA as an ALI prevention agent. The findings of this investigation, as well as associated ancillary studies, will be disseminated in the form of oral and abstract presentations at major national and international medical specialty meetings. The primary objective and other significant findings will also be presented in manuscript form. All final, published manuscripts resulting from this protocol will be submitted to Pub Med Central in accordance with the National Institute of Health Public Access Policy.
acute lung injury; acute respiratory ditress syndrome; aspirin; critical illness; prevention; clinical trial
The system used by the National Nosocomial Infection Surveillance (NNIS) program to measure risk of surgical site infection uses a score of 3 on the American Society of Anesthesiologists (ASA)-physical status scale as a measure of underlying illness. The chronic disease score measures health status as a function of age, sex, and 29 chronic diseases, inferred from dispensing of prescription drugs. We studied the relationship between the chronic disease score and surgical site infection and whether the score can supplement the NNIS risk index. In a retrospective comparison of 191 patients with surgical site infection and 378 uninfected controls, the chronic disease score and ASA score were highly correlated. The chronic disease score improved prediction of infection by the NNIS risk index and augmented the ASA score for risk adjustment.
Properties of the NO-ASA family of NO-donating NSAIDs (NO-NSAIDs), notably NCX 4016 (mNO-ASA) and NCX 4040 (pNO-ASA), reported in more than a hundred publications, have included positive preclinical data in cancer chemoprevention and therapy. Evidence is presented that the antiproliferative, the chemopreventive (antioxidant/electrophile response element (ARE) activation), and the anti-inflammatory activity of NO-ASA in cell cultures is replicated by X-ASA derivatives that are incapable of acting as NO donors. pBr-ASA and mBr-ASA are conisogenic with NO-ASA, but are not NO donors. The biological activity of pNO-ASA is replicated by pBr-ASA; and both pNO-ASA and pBr-ASA are bioactivated to the same quinone methide electrophile. The biological activity of mNO-ASA is replicated by mBr-ASA; mNO-ASA and mBr-ASA are bioactivated to different benzyl electrophiles. The observed activity is likely initiated by trapping of thiol biomolecules by the quinone and benzyl electrophiles, leading to depletion of GSH and modification of Cys-containing sensor proteins. Whereas all NO-NSAIDs containing the same structural “linker” as NCX 4040 and NCX 4016 are anticipated to possess activity resulting from bioactivation to electrophilic metabolites, this expectation does not extend to other linker structures. Nitrates require metabolic bioactivation to liberate NO bioactivity, which is often poorly replicated in vitro, and NO bioactivity provided by NO-NSAIDs in vivo provides proven therapeutic benefits in mitigation of NSAID gastrotoxicity. The in vivo properties of X-ASA drugs await discovery.
Chemoprevention; quinone oxidoreductase; hybrid drugs; antioxidant response element; quinone methide; nitrates; inflammation; NO-ASA; NO-NSAID
We reported that aspirin (ASA) abnormally prolongs bleeding time (BT) in uremia. The present study was designed to investigate whether the abnormally prolonged post-ASA BT in uremia is due to different ASA pharmacokinetics and bioavailability that might be a consequence of uremic condition, platelet cyclooxygenase is peculiarly sensitive to ASA in uremia, and ASA affects primary hemostasis in uremia by a mechanism independent of cyclooxygenase inhibition. Our results showed that in patients with uremia, but not in normal subjects, ASA markedly prolongs the BT. This effect is transient and depends on the presence of ASA in the blood. The observed differences in ASA kinetic parameters are not an explanation of the exaggerated effect of ASA on primary hemostasis in uremia. The sensitivity of platelet cyclooxygenase to ASA inhibition is comparable in uremics and in normal subjects. The temporal dissociation between ASA-induced prolongation of BT and the effect on platelet thromboxane A2 generation suggests that ASA inhibits platelet function in uremia by a mechanism distinct from cyclooxygenase blocking. This possibility is strengthened by the observation that ibuprofen at a dose that fully inhibits platelet cyclooxygenase activity does not significantly prolong BT.
Enhanced recovery program (ERP) was implemented to optimize the hospital stay in total hip arthroplasty. This study assessed the effects of optimizing preoperative and perioperative care using enhanced recovery (ER) on patients undergoing Total hip arthroplasty.
Materials and Methods:
We compared a prospective group of 64 patients on the ER program with a historic cohort of 63 patients that received conventional care (non ER).
ER patients were discharged earliest from hospital [mean length of stay (LOS) 5.3 days, median 4; P < 0.001] as compared to a mean of 8.3 days among non ER patients. Comparison based on American Association of Anesthesiologists (ASA) grades, preoperative hemoglobin, and body mass index (BMI) revealed that patients with ASA grade 3, preoperative hemoglobin of <14 g/dl, and BMI >30 on ER program spent shorter time in hospital as compared to the non ER's conventionally treated patients with more favorable physiological parameters of ASA grade 1 and 2, preoperative hemoglobin of >14 g/dl, and BMI <30.
The ER protocol is universally beneficial and confers an advantage regardless of the patients’ preoperative condition.
Enhanced recovery program; length of stay; total hip arthroplasty
Intravenous acetaminophen, Ofirmev®, is approved for management of mild to moderate pain, management of moderate to severe pain with adjunctive opioids, and reduction of fever. The product is supplied as a 100 mL glass vial. As stated in the prescribing information, it is recommended to be infused over 15 minutes. This recommendation is related to the formulation propacetamol, the prodrug to acetaminophen, approved in Europe, which caused pain on infusion, and data from the clinical development of acetaminophen. The objective of this retrospective chart review study was to show the lack of side effects of rapidly infusing intravenous acetaminophen. Charts of American Society of Anesthesiology (ASA) Class I–III ambulatory surgical patients who received only acetaminophen in the preoperative setting were reviewed for any infusion-related side effects. Using standard binomial proportion analyses and employing SAS/JMP software, all vital signs were analyzed for statistically significant changes between pre- and postinfusion values. One hundred charts were reviewed. Only one patient had pain on infusion, which lasted 10 seconds. No reported side effects or erythema was seen at the injection site. No infusions had to be slowed or discontinued. The median infusion time was 3:41 minutes. Of the vital signs monitored, only the systolic (P < 0.0001) and diastolic (P < 0.0099) blood pressures had statistically significant changes from pre- to postinfusion; however, they were of no clinical relevance. Acetaminophen can be administered as a rapid infusion with no significant infusion-related side effects or complications.
Myoglobin is a cytoplasmic hemoprotein, expressed solely in cardiac myocytes and oxidative skeletal muscle fibers, that reversibly
binds O2 by its heme residue. Myoglobin is an essential oxygen-storage hemoprotein capable of facilitating oxygen transport and
modulating nitric oxide homeostasis within cardiac and skeletal myocytes. Functionally, myoglobin is well accepted as an O2-
storage protein in muscle, capable of releasing O2 during periods of hypoxia or anoxia. There is no evidence available regarding
active sites, ligand binding sites, antigenic determinants and the ASA value of myoglobin in Channa striata. We further document
the predicted active sites in the structural model with solvent exposed ASA residues. During this study, the model was built by
CPH program and validated through PROCHECK, Verify 3D, ERRAT and ProSA for reliability. The active sites were predicted in
the model with further ASA analysis of active site residues. The discussed information thus provides the predicted active sites,
ligand binding sites, antigenic determinants and ASA values of myoglobin model in Channa striata.
Validation; Active Sites Prediction; Ligand Binding Sites; Antigenic Determinants and ASA analysis
Isolated human colonic epithelial cell suspensions were incubated with either 0.1 mM 5-aminosalicylic acid (5-ASA) or 0.1 mM acetylaminosalicylic acid (Ac-ASA) for up to two hours. Intra- and extracellular 5-ASA and Ac-ASA were measured by high performance liquid chromatography. Mean 5-ASA uptake in one hour was 160.5 nmol/g dry weight, compared with an Ac-ASA uptake of only 5.75 nmol/g dry weight. No unchanged 5-ASA was detected inside the cell. Repeated washing had no effect on the intracellular Ac-ASA concentration. This discrepancy in drug uptake may explain why Ac-ASA seems to be ineffective when given to patients with ulcerative colitis.
A deficiency of arylsulfatase A (ASA) causes metachromatic leukodystrophy (MLD), a lysosomal storage disorder characterized by accumulation of sulfatide, a severe neurological phenotype and early death. The efficacy of enzyme replacement therapy (ERT) has previously been determined in ASA knockout (ASA−/−) mice representing the only available animal model for MLD. Repeated intravenous injection of human ASA (hASA) improved the nervous system pathology and function, but also elicited a progressive humoral immune response leading to treatment resistance, anaphylactic reactions, and high mortality. In contrast to ASA−/− mice, most MLD patients express mutant hASA which may entail immunological tolerance to substituted wildtype hASA and thus protect from immunological complications. To test this notion, a cysteine-to-serine substitution was introduced into the active site of the hASA and the resulting inactive hASA-C69S variant was constitutively expressed in ASA−/− mice. Mice with sub-to supranormal levels of mutant hASA expression were analyzed. All mice, including those showing transgene expression below the limit of detection, were immunologically unresponsive to injected hASA. More than 100-fold overexpression did not induce an overt new phenotype except occasional intralysosomal deposition of minor amounts of glycogen in hepatocytes. Furthermore, long-term, low-dose ERT reduced sulfatide storage in peripheral tissues and the central nervous system indicating that high levels of extracellular mutant hASA do not prevent cellular uptake and lysosomal targeting of substituted wildtype hASA. Due to the tolerance to hASA and maintenance of the MLD-like phenotype, the novel transgenic strain may be particularly advantageous to assess the benefit and risk of long-term ERT.
Various adjuvants are being used with local anesthetics for prolongation of intraoperative and postoperative analgesia. Dexmedetomidine, the highly selective 2 adrenergic agonist is a new neuraxial adjuvant gaining popularity.
Settings and Design:
The study was conducted in prospective, double blind manner. It included 120 American Society of Anesthesiology (ASA) class I and II patients undergoing lower limb surgery under spinal anesthesia after approval from hospital ethics committee with written and informed consent of patients.
Materials and Methods:
The patients were randomly allocated into four groups (30 patients each). Group BS received 12.5 mg hyperbaric bupivacaine with normal saline, group BF received 12.5 mg bupivacaine with 25 g fentanyl, group BC received 12.5 mg of bupivacaine supplemented 30 g clonidine, and group BD received 12.5 mg bupivacaine plus 5 g dexmedetomidine. The onset time to reach peak sensory and motor level, the regression time of sensory and motor block, hemodynamic changes, and side effects were recorded.
Patients in Group BD had significantly longer sensory and motor block times than patients in Groups BC, BF, and BS with Groups BC and BF having comparable duration of sensory and motor block. The mean time of two segment sensory block regression was 147 ± 21 min in Group BD, 117 ± 22 in Group BC, 119 ± 23 in Group BF, and 102 ± 17 in Group BS (P > 0.0001). The regression time of motor block to reach modified Bromage zero (0) was 275 ± 25, 199 ± 26, 196 ± 27, 161 ± 20 in Group BD, BC, BF, and BS, respectively (P > 0.0001). The onset times to reach T8 dermatome and modified Bromage 3 motor block were not significantly different between the groups. Dexmedetomidine group showed significantly less and delayed requirement of rescue analgesic.
Intrathecal dexmedetomidine is associated with prolonged motor and sensory block, hemodynamic stability, and reduced demand of rescue analgesics in 24 h as compared to clonidine, fentanyl, or lone bupivacaine.
α2; adrenoreceptor agonist; bupivacaine; clonidine; dexmedetomidine; fentanyl; spinal anesthesia
Lumbar spine surgery in morbidly obese patients is a challenge to the operating surgeon. The aim of the study was to evaluate the surgical experience in this group of patients using the Synframe retractor system (Synthes, Paoli, PA, USA) as a tool for improved surgical access.
An Institutional Review Board approved retrospective study was conducted on 43 morbidly obese patients undergoing posterior lumbar decompression instrumentation and fusion. Patient selection was based on a BMI of >40. Information acquired included BMI, set up time, procedure time, ASA, intraoperative blood loss and the number of preoperative co-morbidities of each patient. Postoperative complications, length of stay, and pre-operative and postoperative Oswestry disability index (ODI) and visual analogue scale (VAS) were recorded at each postoperative visit. They were compared to 45 age matched controls from our spine database.
The average set-up time (73.5 min), amount of blood loss (average 1,040 mL), length of incision (10.3–14.5 cm) and length of hospital stay (5.4 days) were recorded. The average surgical time was dependent on the procedure and number of levels fused and ranged from 164 to 245 min. These parameters were compared with normal weight patients and noted to be higher.
The surgical experience determined that the Synframe retractor system provided a stable and well-illuminated operative field. It minimized the number of personnel required for assistance and improved surgical access. As may be expected, all the above recorded parameters were greater in the morbidly obese group.
Obesity; Lumbar fusion; Synframe
Recently there has not been a systematic, objective assessment of the metabolic capabilities of the human platelet. A manually curated, functionally tested, and validated biochemical reaction network of platelet metabolism, iAT-PLT-636, was reconstructed using 33 proteomic datasets and 354 literature references. The network contains enzymes mapping to 403 diseases and 231 FDA approved drugs, alluding to an expansive scope of biochemical transformations that may affect or be affected by disease processes in multiple organ systems. The effect of aspirin (ASA) resistance on platelet metabolism was evaluated using constraint-based modeling, which revealed a redirection of glycolytic, fatty acid, and nucleotide metabolism reaction fluxes in order to accommodate eicosanoid synthesis and reactive oxygen species stress. These results were confirmed with independent proteomic data. The construction and availability of iAT-PLT-636 should stimulate further data-driven, systems analysis of platelet metabolism towards the understanding of pathophysiological conditions including, but not strictly limited to, coagulopathies.
The aim of the study was to investigate whether preemptive multimodal analgesia (diclofenac, butorphanol, and lidocaine) was obtained during sagittal split ramus osteotomy (SSRO). Following institutional approval and informed consent, 82 healthy patients (ASA-I) undergoing SSRO were randomly assigned to 1 of 2 groups, the preemptive multimodal analgesia group (group P, n = 41) and the control group (group C, n = 41). This study was conducted in a double-blind manner. Patients in group P received 50 mg rectal diclofenac sodium, 10 micrograms/kg intravenous 0.1% butorphanol tartrate, and 1% lidocaine solution containing 10 micrograms/mL epinephrine for regional anesthesia and for bilateral inferior alveolar nerve blocks before the start of surgery. Postoperative pain intensity at rest (POPI) was assessed on a numerical rating score (NRS) in the postanesthesia care unit (PACU) and on a visual analogue scale (VAS) at the first water intake (FWI) and at 24, 48, and 72 hours after extubation. POPI in the PACU was significantly lower in group P than in group C, whereas there were no significant differences at FWI, 24, 48, and 72 hours after extubation in both groups. Preemptive multimodal analgesia was not observed in this study.
Significant intra-procedural adverse events(AE) are reported in children who receive anesthesia for procedures outside the Operating Rooms(NORA). No study, so far, has characterized AE in children who receive anesthesia in the operating rooms(ORA) and NORA when anesthesia care is provided by the same team in a consistent manner.
We used the same patient-specific Quality Assurance questionnaires(QAs), to elucidate incidences of intra-operative reported AE for children receiving anesthesia in NORA and ORA locations. Through multivariate logistic regression analysis we assessed the association between patient’s AE risk and procedure’s location while adjusting for ASA status, age and unscheduled nature of the procedure.
After IRB approval, we used returned QAs of patients under 21 years; who received anesthesia from our pediatric anesthesia faculty; from May 1, 2006 through September 30, 2007. We analyzed QA data on: service location, unscheduled/schedule procedure, age, ASA status, presence and type of AE. We excluded QAs with incomplete information on date, location, age and ASA status.
We included 8,707 cases, with 3.5% incidence of reported AE. We had 1,898 NORA and 6,808 ORA cases with AE incidence of 2.5% and 3.7% respectively. Multivariate regression analysis revealed that patients with higher ASA status or younger age had higher incidence of reported AE, irrespective of location or unscheduled nature of the procedure. The most common AE type, for both sites, was respiratory-related (1.9%).
Pediatric reported AE incidence was comparable for NORA and ORA locations. Younger age or higher ASA status are associated with increased risk of AE.
anesthesia; pediatric; adverse events; ORA; NORA
Pregabalin has been shown to have analgesic effect in acute pain models. The primary objective was to examine the efficacy a single dose of pregabalin, would have on morphine consumption following lumbar discectomy.
With ethical approval a randomized, placebo-controlled prospective trial was undertaken in 32 patients (ASA I-II, 18-65 years) with radicular low back pain for > 3 months undergoing elective lumbar discectomy. Patients received either oral pregabalin 300 mg (PG Group) or placebo (C Group) one hour before surgery. Pain intensity, the accumulative morphine consumption and adverse effects were recorded for 24 hours following surgery. Functional, psychological and quantitative sensory testing were also assessed.
Fourteen patients out of the 32 recruited were randomized to receive pregabalin. Morphine consumption was reduced (absolute difference of 42.3%) between groups with medium effect size. (Mann-Whitney; U = 52.5, z-score= 2.84, P = 0.004, r = 0.14). This was not associated with a significant difference in the incidence of adverse effects between the two groups. The median pain intensity (VAS) on movement was not significantly different between groups.
A single pre-operative dose of pregabalin (300 mg) did not result in a reduction in pain intensity compared to placebo in this patient cohort but the significant reduction in morphine consumption suggests that a fixed peri-operative dosing regime warrants investigation.
morphine consumption; post-operative pain; pregabalin
The C-MAC® (Karl Storz, Tuttlingen, Germany) has recently been introduced as a new device for videolaryngoscopy guided intubation. The purpose of the present study was to compare for the first time the C-MAC with conventional direct laryngoscopy in 150 patients during routine induction of anaesthesia.
After approval of the institutional review board and written informed consent, 150 patients (ASA I-III) with general anaesthesia were enrolled. Computer-based open crossover randomisation was used to determine the sequence of the three laryngoscopies: Conventional direct laryngoscopy (HEINE Macintosh classic, Herrsching, Germany; blade sizes 3 or 4; DL group), C-MAC size 3 (C-MAC3 group) and C-MAC size 4 (C-MAC4 group) videolaryngoscopy, respectively. After 50 patients, laryngoscopy technique in the C-MAC4 group was changed to the straight blade technique described by Miller (C-MAC4/SBT).
Including all 150 patients (70 male, aged (median [range]) 53 [20-82] years, 80 [48-179] kg), there was no difference of glottic view between DL, C-MAC3, C-MAC4, and C-MAC4/SBT groups; however, worst glottic view (C/L 4) was only seen with DL, but not with C-MAC videolaryngoscopy. In the subgroup of patients that had suboptimal glottic view with DL (C/L≥2a; n = 24), glottic view was improved in the C-MAC4/SBT group; C/L class improved by three classes in 5 patients, by two classes in 2 patients, by one class in 8 patients, remained unchanged in 8 patients, or decreased by two classes in 1 patient. The median (range) time taken for tracheal intubation in the DL, C-MAC3, C-MAC4 and C-MAC4/SBT groups was 8 sec (2-91 sec; n = 44), 10 sec (2-60 sec; n = 37), 8 sec (5-80 sec; n = 18) and 12 sec (2-70 sec; n = 51), respectively.
Combining the benefits of conventional direct laryngoscopy and videolaryngoscopy in one device, the C-MAC may serve as a standard intubation device for both routine airway management and educational purposes. However, in patients with suboptimal glottic view (C/L≥2a), the C-MAC size 4 with straight blade technique may reduce the number of C/L 3 or C/L 4 views, and therefore facilitate intubation. Further studies on patients with difficult airway should be performed to confirm these findings.
The incidence of difficulty in tracheal intubation has been reported to range from 0.5 to 18% in patients undergoing surgery. We aimed to elucidate the role of upper lip bite test (ULBT) with other prevailing tests, hyomental/thyrosternal distances (HMD/TSD), and the mandible length (ML) and their possible correlation in predicting difficulty in intubation. After institutional approval and informed consent were obtained, 300 consecutive patients aged 20–60 years of ASA physical status I and II, scheduled for elective surgical procedures requiring tracheal intubation and meeting the inclusion criteria, were enrolled in this study. Each patient was evaluated regarding ULBT, HMD, TSD and ML. Laryngoscopy was assessed by an attending anaesthesiologist blinded to the measurements. The laryngoscopic result was graded according to Cormack and Lehane’s Grading system. The negative predictive value (NPV) and positive predictive value (PPV) of ULBT were found to be 94 and 100%, respectively. These corresponding figures for TSD were 88.5 and 0%, respectively. Specificities for ULBT, HMD, ML and TSD were 100, 98.9, 98.9 and 98.1%, respectively. ULBT class and laryngoscopic grading showed the greatest agreement (kappa = 0.61, P < 0.001). An agreement between laryngoscopic grading and HMD and ML also existed (0.003 and <0.001, respectively), but was comparatively weaker. The high specificity, NPV, PPV and accuracy of ULBT as revealed in this study could be a good rationale for its application in the prediction of difficulty or easiness in intubation. ML > 9 cm and HMD > 3.5 cm were good predictors of negative difficult intubation.
Difficult intubation; difficult laryngoscopy; endotracheal intubation; predictive airway tests
The aminosalicylates (5-ASA; also referred to as mesalamine-based agents) are considered as first-line in the maintenance of remission of mild to moderate ulcerative colitis (UC). Traditionally these agents have required a large pill burden and multiple daily dosing regimens which may account for the low adherence rates, especially in patients in remission. Extended-release mesalamine is the first once daily mesalamine product approved by the Food and Drug Administration for the maintenance of UC remission. This review will examine the pharmacokinetics, dosing, efficacy, and safety data of extended-release mesalamine, and discuss the potential role of improving medication compliance and decreasing costs in UC maintenance.
ulcerative colitis; 5-ASA; mesalamine; adherence; compliance; quality of life; costs
According to the guidelines of the European Stroke Organization (ESO) and the American Stroke Association (ASA), acute stroke patients should be managed at stroke units that include well organized pre- and in-hospital care. In ischemic stroke the restoration of blood flow has to occur within a limited time window that is accomplished by fibrinolytic therapy. Newer generation thrombolytic agents (alteplase, pro-urokinase, reteplase, tenecteplase, desmoteplase) have shorter half-life and are more fibrin-specific. Only alteplase has Food and Drug Administration (FDA) approval for the treatment of acute stroke (1996). The National Institute of Neurological Disorders and Stroke (NINDS) trial proved that alteplase was effective in all subtypes of ischemic strokes within the first 3 h. In the European cooperative acute stroke study III trial, intravenous (IV) alteplase therapy was found to be safe and effective (with some restrictions) if applied within the first 3–4.5 h. In middle cerebral artery (MCA) occlusion additional transcranial Doppler insonication may improve the breakdown of the blood clot. According to the ESO and ASA guidelines, intra-arterial (IA) thrombolysis is an option for recanalization within 6 h of MCA occlusion. Further trials on the IA therapy are needed, as previous studies have involved relatively small number of patients (compared to IV trials) and the optimal IA dose of alteplase has not been determined (20–30 mg is used most commonly in 2 h). Patients undergoing combined (IV + IA) thrombolysis had significantly better outcome than the placebo group or the IV therapy alone in the NINDS trial (Interventional Management of Stroke trials). If thrombolysis fails or it is contraindicated, mechanical devices [e.g., mechanical embolus removal in cerebral ischemia (MERCI)- approved in 2004] might be used to remove the occluding clot. Stenting can also be an option in case of acute internal carotid artery occlusion in the future. An intra-aortic balloon was used to increase the collateral blood flow in the Safety and Efficacy of NeuroFlo™ Technology in Ischemic Stroke trial (results are under evaluation). Currently, there is no approved effective neuroprotective drug.
intravenous thrombolysis; intra-arterial thrombolysis; acute stroke; mechanism of recanalization; thrombectomy; alteplase; stroke unit; therapeutic time window
The aim of this randomized, controlled study was to compare the sedoanalgesic effects of ketamine-dexmedetomidine and ketamine-midazolam on dressing changes of burn patients.
Materials and Methods:
Following Ethics Committee approval and informed patient consent, 90 ASA physical statuses I and II adult burn patients were included in the study. Patients were randomly divided into three groups. Ten minutes before dressing change, the dexmedetomidine group (group KD) (n = 30) received a continuous infusion of dexmedetomidine at a rate of 1 μg kg-1, the midazolam group (group KM) (n = 30) received a continuous infusion of midazolam at a rate of 0.05 mg kg-1 and the saline group (group KS) (n = 30) received a continuous infusion of saline intravenously. One minute before dressing change, each patient was administered 1 mg kg-1 ketamine intravenously. Hemodynamic variables, pain and sedation scores, the number of patients requiring additional ketamine, time to dressing change and recovery time were recorded.
Systolic blood pressure (SBP) values were significantly lower at, before and after ketamine administration; and 5, 10 and 15 minutes after the procedure in group KD in comparison with the other groups (P <0.05). There was no significant difference in pain scores among the groups during the study period. Sedation scores were significantly higher in group KD than in groups KM and KS at the end of the first hour (P <0.05). Time to dressing change and recovery time were similar in all the groups
In burn patients undergoing dressing changes, although both combinations ketamine-dexmedetomidine and ketamine-midazolam offered an effective sedoanalgesia without causing any significant side effect, the former resulted in higher sedation and lower hemodynamic discrepancy.
Burn; dexmedetomidine; dressing changes; ketamine; midazolam
Post operative analgesia in patients undergoing lower limb surgery is very essential for immediate postoperative pain relief which can be provided by oral or parentral medication, epidural analgesia, local blocks etc.The study was designed to evaluate the efficacy of epidural butorphanol and tramadol for postoperative pain relief.
Patients & Methods:
This was randomized, prospective, double blind study was conducted on 60 patients, ASA grade I&II, age 18-60 undergoing lower limb surgeries after approval from hospital ethics committee. Group allocation - Group I I (n=30) received 2 mg butorphanol as bolus epidurally, 1 mg for top up dose. Group II (n=30) received 100mg tramadol as bolus, 50 mg for top up. All the drugs were diluted to 10 ml normal saline & the observer was blinded to the drugs given. Postoperatively VAS, sedation score, vitals & side effects were observed. Top ups were given on achieving VAS>4. Diclofenac 75mg was given as rescue analgesia.
Duration of analgesia was 5.35±0.29 hr and 6.25±1.58 hrs in Butorphanol and Tramadol groups respectively and the difference was found to be statistically significant. Pain scores were also significantly lower statistically in Group I as compared to Group II. Sedation scores were significantly higher in butorphanol group, whereas nausea vomiting was seen in tramadol group only (4 patients).No other side effects were observed.
Both butorphanol and tramadol were effective for relieving postoperative pain, however quality of analgesia & patient satisfaction was more with butorphanol.
Epidural; Tramadol; Butorphanol; Post-operative Pain
A microemulsion propofol causes a high incidence of pain during intravenous injection. In this study, we investigated the effect of ramosetron on pain induced by microemulsion propofol injection.
After prospective power analysis and institutional review board approval, a total of 200 ASA I and II patients undergoing general anesthesia were divided into 4 groups. They received one of the following intravenously after tourniquet application on the forearm 1 min before induction of anesthesia using microemulsion propofol; normal saline (Group N, n = 50), lidocaine 20 mg (Group L, n = 50), ramosetron 0.3 mg (Group R, n = 50) and lidocaine 20 mg plus ramosetron 0.3 mg (Group LR, n = 50) diluted into a 5 ml solution. The occlusion was released after 30 seconds and microemulsion propofol was injected over 10-15 seconds. The patients were observed and asked immediately if they had pain in the arm, and their responses were assessed.
The incidence of pain in groups N, L, R and LR was 96%, 76%, 60% and 38%, respectively (P < 0.008). Two patients in Group LR (4.0%) and nine in Group R (18.0%) had moderate to severe pain, which was significantly lower than pain in Groups N (84.0%), L (40.0%) and R (P < 0.008).
Pretreatment with ramosetron 0.3 mg with or without lidocaine 20 mg with a tourniquet on the forearm 30 seconds before the injection of microemulsion propofol is more effective than lidocaine 20 mg or normal saline in preventing pain from a microemulsion propofol injection.
Injection; Microemulsion; Pain; Propofol; Ramosetron
The postoperative cognitive function is impaired in elderly patients after general anaesthesia. The fast recovery after xenon anaesthesia was hypothesized to be advantageous in this scenario. We compared early postoperative cognitive function after xenon and sevoflurane anaesthesia in this study.
The study was approved by the local ethics committee and written informed consent was obtained from each patient. Patients aged 65-75 years (ASA I-III) scheduled for elective surgery (duration 60-180 min) were enrolled. Investigators performing cognitive testing and patients were blinded towards allocation to either xenon or sevoflurane anaesthesia. Baseline assessment of cognitive function was carried out 12-24 h before the operation. The results were compared to follow-up tests 6-12 and 66-72 h after surgery. Primary outcome parameter was the subtest "Alertness" of the computerized Test of Attentional Performance (TAP). Secondary outcome parameters included further subtests of the TAP, several Paper-Pencil-Tests, emergence times from anaesthesia, modified Aldrete scores and patients' well-being.
40 patients were randomized and equally allocated to both groups. No significant differences were found in the TAP or the Paper-Pencil-Tests at 6-12 and 66-72 h after the operation. All emergence times were faster after xenon anaesthesia. The modified Aldrete scores were significantly higher during the first hour in the xenon group. No difference in well-being could be detected between both groups.
The results show no difference in the incidence of postoperative cognitive dysfunction (POCD) after xenon or sevoflurane anaesthesia. Emergence from general anaesthesia was faster in the xenon group.
To determine how pretreatment with magnesium sulfate (MgSO4) potentiates neuromuscular blocking agents. We investigated how the onset and recovery characteristics of cisatracurium are changed by pretreatment with MgSO4.
After Institutional Review Board approval, a total of 48 ASA I and II patients were devided into 2 groups. Patients in each group received either the MgSO4 30 mg/kg (group M) in 0.9% normal saline (total volume 100 ml) or 0.9% normal saline (control group C) alone intravenously for 15 min before induction of anesthesia with propofol, remifentanil and cisatracurium 0.15 mg/kg. Anesthesia was maintained with propofol and remifentanil. Electromyographical responses were measured by train-of-four. Lag time, onset time, total recovery time, clinical duration, recovery index, and recovery time were measured. The mean arterial blood pressure, heart rate, and ionized magnesium were also measured.
The lag time and onset time were significantly shorter in the MgSO4 group than the control group (P < 0.05). Recovery index, recovery time, clinical duration, and total recovery time showed no significant differences in the MgSO4 group compared to the control group (P > 0.05). Mean arterial pressure was more significantly increased in the MgSO4 group than in the control group at the time point immediately after the administration of MgSO4. Heart rate showed no significant changes in both groups. The concentrations of ionized magnesium were significantly more increased at the all time point (P < 0.05).
MgSO4 results in about 29% shortening of onset time of cisatracurium (0.15 mg/kg) without prolongation on the recovery of neuromuscular block.
Cisatracurium; Magnesium sulfate; Onset; Recovery
This study was designed to measure in vivo effects of propofol, isoflurane and sevoflurane on apoptosis by measuring caspase-3 and tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) blood level as apoptotic markers.
After obtaining ethical committee approval and informed written consents, sixty adult patients ASA I scheduled for open cholecystectomy participated in this study. They were randomally allocated into one of three equal groups to receive propofol infusion, low-flow isoflurane or sevoflurane for maintenance of anesthesia. Venous blood samples were collected preoperatively, immediately postoperative and after 24 hours to measure hemoglobin, hematocrit, creatinine, liver enzymes, serum TRAIL and caspase-3 levels.
There was no significant difference in hematological markers and serum creatinine. Liver enzymes showed significant postoperative rise (P < 0.05). In Propofol group, TRAIL and caspase-3 levels were significantly elevated immediately postoperative then decreased significantly after 24-hours (P < 0.05). In Isoflurane group, immediate postoperative level of TRAIL was significantly higher than 24 hours reading and significantly lower than its level in Propofol group at the same timing meanwhile caspase-3 levels were comparable at different timings. In Sevoflurane group, TRAIL and caspase-3 levels increased significantly in both postoperative samples than preoperative level and than those of Isoflurane and Propofol groups after 24 hours concerning TRAIL (P & 0.05).
This study concluded that isoflurane is superior and sevoflurane is the least effective among the three anesthetics in protection against apoptosis. This study neither proved nor excluded propofol-induced apoptosis. Further studies are required during lengthy procedure and in compromised patients.
Apoptosis; In vivo; Isoflurane; Propofol; Sevoflurane