Continuous pralidoxime infusion versus repeated bolus injection to treat organophosphorus pesticide poisoning: a randomised controlled trial. Pralidoxime in acute organophosphorus insecticide poisoning--a randomised controlled trial. Optimal dose of intravenous pantoprazole in patients with peptic ulcer bleeding requiring endoscopic hemostasis in Korea. Can remifentanil be a better choice than propofol for colonoscopy during monitored anesthesia care? Controlled, double-blind, multicentre clinical trial to investigate long-term tolerability and efficacy of trospium chloride in patients with detrusor instability. Incidence of intermediate syndrome in organophosphorous poisoning. Biochemical and clinical profile after organophosphorus poisoning--a placebo-controlled trial using pralidoxime. The effect of preoperative dexamethasone on the immediate and delayed postoperative morbidity in children undergoing adenotonsillectomy. Selective decontamination of the colon before elective colorectal surgery. West of Scotland Surgical Infection Study Group.
The role of oximes for the treatment of organophosphorus pesticide poisoning has not been conclusively established. We aimed to assess the effectiveness of a constant pralidoxime infusion compared with repeated bolus doses to treat patients with moderately severe poisoning from organophosphorus pesticides.
                200 patients were recruited to our single-centre, open randomised controlled trial after moderately severe poisoning by anticholinesterase pesticide. All were given a 2 g loading dose of pralidoxime over 30 min. Patients were then randomly assigned to control and study groups. Controls were given a bolus dose of 1 g pralidoxime over 1 h every 4 h for 48 h. The study group had a constant infusion of 1 g over an hour every hour for 48 h. Thereafter, all patients were given 1 g every 4 h until they could be weaned from ventilators. Analysis was by intention to treat. Primary outcome measures were median atropine dose needed within 24 h, proportion of patients who needed intubation, and number of days on ventilation. The study is registered at http://www.clinicaltrials.gov with the identifier NCT00333944.
                100 patients were assigned the high-dose regimen, and 100 the control regimen. There were no drop-outs. Patients receiving the high-dose pralidoxime regimen required less atropine during the first 24 h than controls (median 6 mg vs 30 mg; difference 24 mg [95% CI 24-26, p<0.0001]). 88 (88%) and 64 (64%) of controls and high-dose patients, respectively, needed intubation during admission to hospital (relative risk=0.72, 0.62-0.86, p=0.0001). Control patients required ventilatory support for longer (median 10 days vs 5 days; difference 5 days [5-6, p<0.0001]).
                A high-dose regimen of pralidoxime, consisting of a constant infusion of 1 g/h for 48 h after a 2 g loading dose, reduces morbidity and mortality in moderately severe cases of acute organophosphorus-pesticide poisoning. Poisoning with organophosphorus (OP) insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote's effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit.
                We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receive pralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 0.88-3.26, p = 0.12). Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 [21.5%], placebo 24/114 [21.1%], adjusted HR 1.27 [95% CI 0.71-2.29]). To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit.
                Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required. The lowest effective dose of proton pump inhibitors (PPI) for prevention of peptic ulcer rebleeding remains unclear. The objective of the present study was to evaluate whether low-dose PPI has a similar efficacy to high-dose i.v. administration for maintaining intragastric pH above 6.
                Sixty-one patients with bleeding ulcers were randomized into one of three groups after endoscopic hemostasis: pantoprazole 80 mg bolus followed by 8 mg/h; 40 mg, 4 mg/h infusion; and bolus injection of 40 mg every 24 h. Intragastric pH values and rebleeding rates were measured. In addition, pharmacokinetic parameters and association with CYP2C19 polymorphisms and H. pylori infection were assessed.
                Mean percentage of time with intragastric pH > 6, and the proportion of patients with pH > 6 for more than 60% of the time were significantly higher in the 40 mg, 4 mg/h infusion group compared to the 40 mg bolus injection. There was no significant difference between the 80 mg, 8 mg/h and the 40 mg, 4 mg/h groups. In the H. pylori (-) group, only 40% of patients that received continuous infusion reached the target pH > 6 for more than 60% of the time; this was significantly lower than the H. pylori (+) group, 87.5% (P = 0.026).
                A continuous infusion, regardless of high or low dose, was more effective for acid suppression than a 40 mg bolus PPI injection in Korea. H. pylori infection was an important factor for the maintenance of an intragastric pH > 6. This prospective, randomized trial was designed to test the hypothesis that continuous infusion of low-dose remifentanil can provide effective analgesia, sedation, amnesia, patient comfort and stable recovery profile without respiratory depression when compared with propofol infusion during colonoscopy.
                One hundred patients were randomly assigned to receive either remifentanil (group R, 0.5 microg/kg followed by 0.05 microg/kg/min, n = 50) or propofol (group P, 0.5 mg/kg followed by 50 microg/kg/min, n = 50). Supplemental doses of remifentanil 12.5 microg in group R and propofol 10 mg in group P were given to treat complaints of moderate to severe pain and discomfort. Hemodynamic and respiratory data, pain, discomfort and sedation scores, patient and gastroenterologist satisfaction and recovery profiles were recorded.
                The duration of colonoscopy was longer in group P. The mean arterial pressure, heart rate and end-tidal CO2 remained stable during the procedure and were comparable between the groups. After bolus injection of the study drugs, the respiratory rate and oxygen saturation values were lower in group R than in group P. Only one patient in group R required airway support. Pain and discomfort scores were better in group R than in group P. Sedation levels were higher in group P than in group R. Group P needed more supplemental doses than group R. The time to reach an Aldrete score of nine or more was shorter in group R, but discharge times were similar in the two groups. Amnesia was better in group P. Nausea and vomiting were more frequent in group R during the recovery phase.
                Low-dose remifentanil infusion with intermittent bolus injections can provide adequate sedation, amnesia and better analgesia than propofol infusion during colonoscopy. However, remifentanil-induced nausea and vomiting may be a problem during the recovery phase. Our objectives were to ascertain the tolerability and efficacy of trospium chloride in doses of 20 mg twice daily for long-term therapy (52 weeks) in patients with urge syndrome. The trial comprised a total of 358 patients with urge syndrome or urge incontinence. After randomisation in the ratio of 3:1, participants were treated continuously for 52 weeks with either trospium chloride (20 mg twice daily) or oxybutynin (5 mg twice daily). At intervals of 4-8 weeks, patients were physically examined with measurements of blood pressure and pulse rate, were questioned about any adverse events, checked for compliance and underwent relevant laboratory tests. As an additional safety measure, an ECG was made at 26 and 52 weeks. Urodynamic measurements were performed at the beginning, and at 26 and 52 weeks to determine the maximal cystometric bladder capacity. Among others things, the frequencies of micturition, incontinence and number of urgency events were recorded in patient diary protocols in weeks 0, 2, 26 and 52. The evaluation of vital parameters, laboratory results and ECGs did not show any relevant changes attributable to the action of the anticholinergics. Analysis of the micturition diary clearly indicated a reduction of the micturition frequency, incontinence frequency, and a reduction of the number of urgencies in both treatment groups. Mean maximum cystometric bladder capacity increased during treatment with trospium chloride by 92 ml after 26 weeks and 115 ml after 52 weeks (P=0.001). Further comparison with oxybutynin did not reveal any statistically significant differences in urodynamic variables between the drugs. Adverse events occurred in 64.8% of the patients treated with trospium chloride and 76.7% of those treated with oxybutynin. The main symptom encountered in both treatment group was dryness of the mouth. For patients on trospium chloride, the estimated risk of an unexpected adverse event was 0.027 per patient per week for all adverse events and 0.009 for dryness of the mouth, resulting in a considerably lower risk during treatment given with trospium chloride than with oxybutynin (0.045 and 0.021, respectively). An overall assessment for each of the drugs reveals a comparable efficacy level and a better benefit-risk ratio for trospium chloride than for oxybutynin due to better tolerability. Seventy two patients admitted to the Intensive Care Unit following ingestion of organophosphorus compounds were studied prospectively with two different doses of pralidoxime (PAM). One group received 1 gm immediately after admission and no further PAM and the other group received infusion of PAM, 1 gm 8 hourly for four days (total 12 gms). The incidence of type II paralysis or intermediate syndrome was 47%. We observed a higher incidence in the 4 days of infusion of PAM group (61%) (20 patients) as compared to the single Bolus dose group (39%) (13 patients). Relative risk 1.48 (confidence interval = 0.9-2.4). Organophosphorus (OP) compounds are the most common suicidal poison in developing countries and mortality continues to be high.
                A study was done to see butyryl cholinesterase (BuChE) profile after OP poisoning in pralidoxime (P2AM) and placebo treated cases. Highest recommended dose of P2AM was used to study the reactivation of cholinesterase. Clinical outcomes like, correlation of BuChE and severity of poisoning, mortality and complications like Type I and II paralysis, need for ventilation and ICU stay were also studied.
                Twenty one cases of moderate and severe poisoning with OP compounds were included in the study. Mean BuChE levels came up gradually over 6-7 days, some taking up to two weeks. There was no. difference between the treatment and placebo groups. BuChE levels did not correlate with severity of poisoning nor did it correlate with Type I or II paralysis, need for ventilation, ICU stay or mortality.
                Treatment with P2AM does not make any difference in BuChE reactivation or complications of moderate and severe OP poisoning. We have not been using P2AM for OP poisoning in our medical ICU with good patient outcomes. In this prospective, randomized, double-blind, placebo-controlled study, we examined the effect of preoperative dexamethasone on postoperative nausea and vomiting (PONV) and 24-h recovery in children undergoing tonsillectomy. One hundred thirty children, 2-12 yr of age, ASA physical status I or II, completed the study. All children received oral midazolam 0.5-0.6 mg/kg preoperatively. Anesthesia was induced with halothane and nitrous oxide in 60% oxygen and maintained with nitrous oxide and isoflurane. Intubation was facilitated by mivacurium 0.2 mg/kg. Each child received fentanyl 1 microgram/kg i.v. before initiation of surgery, as well as dexamethasone 1 mg/kg (maximal dose 25 mg) (steroid group) or an equal volume of saline (control group). Intraoperative fluids were standardized to 25-30 mL/kg lactated Ringer's solution. All tonsillectomies were performed under the supervision of one attending surgeon using an electrodissection technique. Postoperatively, fentanyl and acetaminophen with codeine elixir were administered as needed for pain. Rescue antiemetics were administered when a child experienced two episodes of retching and/or vomiting. Before home discharge, the incidence of PONV, need for rescue antiemetics, quality or oral intake, and analgesic requirements did not differ between groups. However, during the 24 h after discharge, more patients in the control group experienced PONV (62% vs 24% in the steroid group) and complained of poor oral intake. Additionally, more children in the control group (8% vs 0% in the steroid group) returned to the hospital for the management of PONV and/or poor oral intake. The preoperative administration of dexamethasone significantly decreased the incidence of PONV over the 24 h after home discharge in these children. Implications: In this double blind, placebo-controlled study, we examined the efficacy of a single large dose (1 mg/kg; maximal dose 25 mg) of preoperative dexamethasone on posttonsillectomy postoperative nausea and vomiting (PONV) in children 2-12 yr of age undergoing tonsillectomy. Compared with placebo, dexamethasone significantly decreased the incidence of PONV in the 24 h after discharge, improved oral intake, decreased the frequency of parental phone calls, and resulted in no hospital returns for the management of PONV and/or poor oral intake. The controversy over the route of administration of antibiotic prophylaxis in patients undergoing elective colorectal operations persists for oral, parenteral, and a combination of the two routes. The oral antibiotics commonly administered for colorectal prophylaxis, neomycin and eythromycin base, are not absorbed in the gastrointestinal tract (GIT). However, the 4-fluoroquinolones are absorbed in the upper GIT and are excreted in part by the colonic mucosa. Their action is then to remove, or severely depress, the gram-negative aerobic bacilli leaving the anaerobic flora unaffected. This action is the principle of selective decontamination. We have assessed the efficacy of oral ciprofloxacin in a prospective randomized clinical trial in which all patients received piperacillin 4 g i.v. as single-dose parenteral prophylaxis. A group of 327 evaluable patients were randomized to receive ciprofloxacin 500 mg b.i.d. with the preoperative cathartic (group OA, n = 159) or no oral antibiotic (group NOA, n = 168). Postoperative wound infection occurred in 18 (11.3%) patients in group OA and 39 (23.2%) patients in group NOA (chi 2 = 7.2, p = 0.007). Operation-related infection of any type occurred in 23 (14.5%) patients in group OA compared with 55 (32.7%) in group NOA (chi 2 = 14.0, p = 0.0002). The median postoperative hospital stay was 11 days (interquartile range 4.5 days) for group OA and 12 days (interquartile range 8 days) for group NOA (Mann Whitney U test, p = 0.005). Ignoring the treatment group, the median postoperative hospital stay was 17 days (interquartile range 10 days) for infected patients and 11 days (interquartile range 4 days) for those not infected.(ABSTRACT TRUNCATED AT 250 WORDS)
Current evidence is insufficient to indicate whether oximes are harmful or beneficial. The WHO recommended regimen (30 mg/kg pralidoxime chloride bolus followed by 8 mg/kg/hr infusion) is not supported. Further RCTs are required to examine other strategies and regimens. There are many theoretical and practical reasons why oximes may not be useful, particularly for late presentations of dimethyl OP and those with a large excess of OP that simply re-inhibits reactivated enzymes. Future studies should screen for patient sub-groups that may benefit and may need flexible dosing strategies as clinical effectiveness and doses may depend on the type of OP.