Effectiveness and Cost-Effectiveness of Team-Based Care for Hypertension: A Meta-Analysis and Simulation Study.

BACKGROUND: Team-based care (TBC), a team of ≥2 healthcare professionals working collaboratively toward a shared clinical goal, is a recommended strategy to manage blood pressure (BP). However, the most effective and cost-effective TBC strategy is unknown. METHODS: A meta-analysis of clinical trials in US adults (aged ≥20 years) with uncontrolled hypertension (≥140/90 mm Hg) was performed to estimate the systolic BP reduction for TBC strategies versus usual care at 12 months. TBC strategies were stratified by the inclusion of a nonphysician team member who could titrate antihypertensive medications. The validated BP Control Model-Cardiovascular Disease Policy Model was used to project the expected BP reductions out to 10 years and simulate cardiovascular disease events, direct healthcare costs, quality-adjusted life years, and cost-effectiveness of TBC with physician and nonphysician titration. RESULTS: Among 19 studies comprising 5993 participants, the 12-month systolic BP change versus usual care was -5.0 (95% CI, -7.9 to -2.2) mm Hg for TBC with physician titration and -10.5 (-16.2 to -4.8) mm Hg for TBC with nonphysician titration. Relative to usual care at 10 years, TBC with nonphysician titration was estimated to cost $95 (95% uncertainty interval, -$563 to $664) more per patient and gain 0.022 (0.003-0.042) quality-adjusted life years, costing $4400/quality-adjusted life year gained. TBC with physician titration was estimated to cost more and gain fewer quality-adjusted life years than TBC with nonphysician titration. CONCLUSIONS: TBC with nonphysician titration yields superior hypertension outcomes compared with other strategies and is a cost-effective way to reduce hypertension-related morbidity and mortality in the United States.

Assessment of the effects of dexmedetomidine on outcomes of traumatic brain injury using propensity score analysis.

BACKGROUND: Dexmedetomidine was found to be protective against traumatic brain injury (TBI) in animal studies and safe for use in previous clinical studies, but whether it improves TBI patient survival remains to be determined. We sought to answer this question by analyzing data from the MIMIC clinical database. METHODS: Data for TBI patients from the MIMIC III and MIMIC IV databases were extracted and divided into a dexmedetomidine group and a control group. In the former group, dexmedetomidine was used for sedation, while in the latter, it was not used. Parameters including patient age, the Acute Physiology score III, the Glasgow Coma Scale, other sedatives used, and pupillary response within 24 h were employed in propensity score matching to achieve a balance between groups for further analysis. In-hospital survival and 6-month survival were analyzed by Kaplan-Meier survival analysis and compared by log-rank test. Cox regression was used repeatedly for the univariate analysis, the multivariate analysis, the propensity score-matched analysis, and the inverse probability of treatment weighted analysis of survival data. Meanwhile, the influences of hypotension, bradycardia, infection, and seizure on outcome were also analyzed. RESULTS: Different types of survival analyses demonstrated the same trend. Dexmedetomidine significantly improved TBI patient survival. It caused no more incidents of hypotension, infection, and seizure. Hypotension was not correlated with in-hospital mortality, but was significantly correlated with 6-month mortality. CONCLUSIONS: Dexmedetomidine may improve the survival of TBI patients. It should be used with careful avoidance of hypotension.

The pathophysiology of sepsis - 2021 update: Part 2, organ dysfunction and assessment.

PURPOSE: This is the second article in a 2-part series discussing the pathophysiology of sepsis. Part 1 of the series reviewed the immunologic response and overlapping pathways of inflammation and coagulation that contribute to the widespread organ dysfunction. In this article (part 2), major organ systems and their dysfunction in sepsis are reviewed, with discussion of scoring systems used to identify patterns and abnormal vital signs and laboratory values associated with sepsis. SUMMARY: Sepsis is a dysregulated host response to infection that produces significant morbidity, and patients with shock due to sepsis have circulatory and cellular and metabolic abnormalities that lead to a higher mortality. Cardiovascular dysfunction produces vasodilation, reduced cardiac output and hypotension/shock requiring fluids, vasopressors, and advanced hemodynamic monitoring. Respiratory dysfunction may require mechanical ventilation and attention to volume status. Renal dysfunction is a frequent manifestation of sepsis. Hematologic dysfunction produces low platelets and either elevation or reduction of leukocytes, so consideration of the neutrophil:lymphocyte ratio may be useful. Procoagulant and antifibrinolytic activity leads to coagulation that is stimulated by inflammation. Hepatic dysfunction manifest as elevated bilirubin is often a late finding in sepsis and may cause reductions in production of essential proteins. Neurologic dysfunction may result from local endothelial injury and systemic inflammation through activity of the vagus nerve. CONCLUSION: Timely recognition and team response with efficient use of therapies can improve patient outcome, and pharmacists with a complete understanding of the pathophysiologic mechanisms and treatments are valuable members of that team.

Reduced exposure to vasopressors through permissive hypotension to reduce mortality in critically ill people aged 65 and over: the 65 RCT.

BACKGROUND: Vasopressors are administered to critical care patients to avoid hypotension, which is associated with myocardial injury, kidney injury and death. However, they work by causing vasoconstriction, which may reduce blood flow and cause other adverse effects. A mean arterial pressure target typically guides administration. An individual patient data meta-analysis (Lamontagne F, Day AG, Meade MO, Cook DJ, Guyatt GH, Hylands M, et al. Pooled analysis of higher versus lower blood pressure targets for vasopressor therapy septic and vasodilatory shock. Intensive Care Med 2018;44:12-21) suggested that greater exposure, through higher mean arterial pressure targets, may increase risk of death in older patients. OBJECTIVE: To estimate the clinical effectiveness and cost-effectiveness of reduced vasopressor exposure through permissive hypotension (i.e. a lower mean arterial pressure target of 60-65 mmHg) in older critically ill patients. DESIGN: A pragmatic, randomised clinical trial with integrated economic evaluation. SETTING: Sixty-five NHS adult general critical care units. PARTICIPANTS: Critically ill patients aged ≥ 65 years receiving vasopressors for vasodilatory hypotension. INTERVENTIONS: Intervention - permissive hypotension (i.e. a mean arterial pressure target of 60-65 mmHg). Control (usual care) - a mean arterial pressure target at the treating clinician's discretion. MAIN OUTCOME MEASURES: The primary clinical outcome was 90-day all-cause mortality. The primary cost-effectiveness outcome was 90-day incremental net monetary benefit. Secondary outcomes included receipt and duration of advanced respiratory and renal support, mortality at critical care and acute hospital discharge, and questionnaire assessment of cognitive decline and health-related quality of life at 90 days and 1 year. RESULTS: Of 2600 patients randomised, 2463 (permissive hypotension, n = 1221; usual care, n = 1242) were analysed for the primary clinical outcome. Permissive hypotension resulted in lower exposure to vasopressors than usual care [mean duration 46.0 vs. 55.9 hours, difference -9.9 hours (95% confidence interval -14.3 to -5.5 hours); total noradrenaline-equivalent dose 31.5 mg vs. 44.3 mg, difference -12.8 mg (95% CI -18.0 mg to -17.6 mg)]. By 90 days, 500 (41.0%) patients in the permissive hypotension group and 544 (43.8%) patients in the usual-care group had died (absolute risk difference -2.85%, 95% confidence interval -6.75% to 1.05%; p = 0.154). Adjustment for prespecified baseline variables resulted in an odds ratio for 90-day mortality of 0.82 (95% confidence interval 0.68 to 0.98) favouring permissive hypotension. There were no significant differences in prespecified secondary outcomes or subgroups; however, patients with chronic hypertension showed a mortality difference favourable to permissive hypotension. At 90 days, permissive hypotension showed similar costs to usual care. However, with higher incremental life-years and quality-adjusted life-years in the permissive hypotension group, the incremental net monetary benefit was positive, but with high statistical uncertainty (£378, 95% confidence interval -£1347 to £2103). LIMITATIONS: The intervention was unblinded, with risk of bias minimised through central allocation concealment and a primary outcome not subject to observer bias. The control group event rate was higher than anticipated. CONCLUSIONS: In critically ill patients aged ≥ 65 years receiving vasopressors for vasodilatory hypotension, permissive hypotension did not significantly reduce 90-day mortality compared with usual care. The absolute treatment effect on 90-day mortality, based on 95% confidence intervals, was between a 6.8-percentage reduction and a 1.1-percentage increase in mortality. FUTURE WORK: Future work should (1) update the individual patient data meta-analysis, (2) explore approaches for evaluating heterogeneity of treatment effect and (3) explore 65 trial conduct, including use of deferred consent, to inform future trials. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10580502. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 14. See the NIHR Journals Library website for further project information.

Low blood pressure is common in patients in intensive care. It is associated with a high risk of death. It can be treated with drugs called vasopressors. These drugs raise blood pressure, but also come with risks and side effects. Usually, a blood pressure target is used to guide how much of the drugs to give to patients. Two previous clinical trials suggested that using a lower blood pressure target (and therefore giving less of the drugs) might reduce the number of deaths among older patients. However, although these results were promising, more research was needed to find out if they were correct. The 65 trial was carried out to test if using a lower blood pressure target really did improve outcomes for older patients. The trial also looked at whether or not it would provide value for money for the NHS. A total of 2600 patients aged ≥ 65 years who had low blood pressure in intensive care joined the trial. Half were randomly assigned to the new lower blood pressure target (less drugs). The other half were assigned to usual care (control group). As we had hoped, patients in the low blood pressure target group received less vasopressor drugs than the usual-care group. After 90 days, 41% of patients in the new low blood pressure target group had died, compared with 44% in the usual-care group. Although fewer patients died in the low blood pressure target group, the difference was small and may have occurred by chance. On average, the new target saved a small amount of money for the NHS. Although we could not prove that use of a lower blood pressure target saves lives for older patients in intensive care, our trial suggests that it might. Receiving less vasopressor drugs appeared safe for patients.

Delayed vasopressor initiation is associated with increased mortality in patients with septic shock.

PURPOSE: Mortality rate for septic shock, despite advancements in knowledge and treatment, remains high. Treatment includes administration of broad-spectrum antibiotics and stabilization of the mean arterial pressure (MAP) with intravenous fluid resuscitation. Fluid-refractory shock warrants vasopressor initiation. There is a paucity of evidence regarding the timing of vasopressor initiation and its effect on patient outcomes. MATERIALS AND METHODS: This retrospective, single-centered, cohort study included patients with septic shock from January 2017 to July 2017. Time from initial hypotension to vasopressor initiation was measured for each patient. The primary outcome was 30-day mortality. RESULTS: Of 530 patients screened,119 patients were included. There were no differences in baseline patient characteristics. Thirty-day mortality was higher in patients who received vasopressors after 6 h (51.1% vs 25%, p < .01). Patients who received vasopressors within the first 6 h had more vasopressor-free hours at 72 h (34.5 h vs 13.1, p = .03) and shorter time to MAP of 65 mmHg (1.5 h vs 3.0, p < .01). CONCLUSION: Vasopressor initiation after 6 h from shock recognition is associated with a significant increase in 30-day mortality. Vasopressor administration within 6 h was associated with shorter time to achievement of MAP goals and higher vasopressor-free hours within the first 72 h.

Hospital costs associated with intraoperative hypotension among non-cardiac surgical patients in the US: a simulation model.

Objective: Recent studies indicate intraoperative hypotension, common in non-cardiac surgical patients, is associated with myocardial injury, acute kidney injury, and mortality. This study extends on these findings by quantifying the association between intraoperative hypotension and hospital expenditures in the US. Methods: Monte Carlo simulations (10,000 trial per simulation) based on current epidemiological and cost outcomes literature were developed for both acute kidney injury (AKI) and myocardial injury in non-cardiac surgery (MINS). For AKI, three models with different epidemiological assumptions (two models based on observational studies and one model based on a randomized control trial [RCT]) estimate the marginal probability of AKI conditional on intraoperative hypotension status. Similar models are also developed for MINS (except for the RCT case). Marginal probabilities of AKI and MINS sequelae (myocardial infarction, congestive heart failure, stroke, cardiac catheterization, and percutaneous coronary intervention) are multiplied by marginal cost estimates for each outcome to evaluate costs associated with intraoperative hypotension. Results: The unadjusted (adjusted) model found hypotension control lowers the absolute probability of AKI by 2.2% (0.7%). Multiplying these probabilities by the marginal cost of AKI, the unadjusted (adjusted) AKI model estimated a cost reduction of $272 [95% CI = $223-$321] ($86 [95% CI = $47-$127]) per patient. The AKI model based on relative risks from the RCT had a mean cost reduction estimate of $281 (95% CI = -$346-$750). The unadjusted (adjusted) MINS model yielded a cost reduction of $186 [95% CI = $73-$393] ($33 [95% CI = $10-$77]) per patient. Conclusions: The model results suggest improved intraoperative hypotension control in a hospital with an annual volume of 10,000 non-cardiac surgical patients is associated with mean cost reductions ranging from $1.2-$4.6 million per year. Since the magnitude of the RCT mean estimate is similar to the unadjusted observational model, the institutional costs are likely at the upper end of this range.

A Monte Carlo simulation estimating US hospital cost reductions associated with hypotension control in septic ICU patients.

OBJECTIVE: This economic analysis extends upon a recent epidemiological study to estimate the association between hypotension control and hospital costs for septic patients in US intensive care units (ICUs). METHODS: A Monte Carlo simulation decision analytic model was developed that accounted for the probability of complications-acute kidney injury and mortality-in septic ICU patients and the cost of each health outcome from the hospital perspective. Probabilities of complications were calculated based on observational data from 110 US hospitals for septic ICU patients (n = 8,782) with various levels of hypotension exposure as measured by mean arterial pressure (MAP, units: mmHg). Costs for acute kidney injury (AKI) and mortality were derived from published literature. Each simulation calculated mean hospital cost reduction and 95% confidence intervals based on 10,000 trials. RESULTS: In the base-case analysis hospital costs for a hypothetical "control" cohort (MAP of 65 mmHg) were $699 less per hospitalization (95% CI: $342-$1,116) relative to a "case" cohort (MAP of 60 mmHg). In the most extreme case considered (45 mmHg vs 65 mmHg), the associated cost reduction was $4,450 (95% CI: $2,020-$7,581). More than 99% of the simulated trials resulted in cost reductions. A conservative institution-level analysis for a hypothetical hospital (which assumes no benefit for increasing MAP above 65 mmHg) estimated a cost decline of $417 for a 5 mmHg increase in MAP per ICU septic patient. These results are applicable to the US only. CONCLUSIONS: Hypotension control (via MAP increases) for patients with sepsis in the ICU is associated with lower hospitalization cost.

Phenylephrine infusion impact on surgical site infections after lower extremity bypass surgery.

OBJECTIVE: Lower extremity bypass (LEB) operations have high rates of surgical site infections (SSI). Phenylephrine is a commonly used vasoconstrictor which may reduce skin blood flow and increase the likelihood of SSI in these patients. We studied the potential effect of phenylephrine infusion during LEB surgery on SSI. METHODS: LEB cases and their demographic data were identified through the Vascular Quality Initiative registry. SSI in this population was identified using the hospital epidemiology surveillance database. Phenylephrine use in this population was identified through chart review. RESULTS: We identified 699 patients who underwent LEB; 82 (11.7%) developed an SSI, and 244 of 698 (35.0%) were treated with phenylephrine infusion. In bivariate analysis, higher body mass index (28.8 kg/m2 vs 27.3 kg/m2; P = .034), diabetes (14.6% vs 9.4%; P = .035), hypertension (12.6% vs 4.7%; P = .038), groin incision (13.2 vs 5.4%; P = .013) and longer procedure times (17.1% for >220 minutes and 8.9% for ≤220 minutes; P = .003) were associated with higher rates of SSI. Whereas phenylephrine infusion exhibited a trend toward a higher rate (14.8% vs 9.9%; P = .057). In the logistic regression model, diabetes (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.0-3.2; P = .032), total procedure time (OR, 1.85; 95% CI, 1.1-3.1; P = .026) and vertical groin incision (OR, 2.6; 95% CI, 1.1-6.5; P = .035) were independent predictors of increased SSI rates, whereas body mass index (OR, 1.04; 95% CI, 0.99-1.08; P = .09), hypertension (OR, 2.5; 95% CI, 0.6-10.9; P = .22), and phenylephrine infusion (OR, 1.08; 95% CI, 0.63-1.85; P = .78) were not independent predictors of increased SSI rates. CONCLUSIONS: Phenylephrine infusion did not increase the risk of SSI in patients who underwent LEB.

Spinal-induced hypotension: Incidence, mechanisms, prophylaxis, and management: Summarizing 20 years of research.

Hypotension commonly occurs in parturients undergoing cesarean delivery under spinal anesthesia. This leads to maternal and neonatal adverse outcomes, including maternal nausea and vomiting and fetal acidosis, and might even lead to cardiovascular collapse if not treated. Arterial dilatation and reduction in systemic vascular resistance are the major contributors to spinal-induced hypotension. Therefore, strategies aimed at expanding the intravascular volume with fluid loading or increasing venous return with lower extremities mechanical compression and lateral tilt have had limited effectiveness in the management of spinal-induced hypotension. Vasopressors are therefore the mainstay for the prophylaxis and treatment of spinal-induced hypotension. Phenylephrine is associated with improved neonatal acid-base status and a lower risk of maternal nausea and vomiting compared with ephedrine and is now considered the vasopressor of choice in obstetric patients. This review discusses the various strategies for managing spinal-induced hypotension with a particular emphasis on the optimal use of vasopressors.

Assessment of an updated double-vasopressor automated system using Nexfin for the maintenance of haemodynamic stability to improve peri-operative outcome during spinal anaesthesia for caesarean section.

Hypotension occurs commonly during spinal anaesthesia for caesarean section, associated with maternal and fetal adverse effects. We developed a double-vasopressor automated system with a two-step algorithm and continuous non-invasive haemodynamic monitoring using the Nexfin device. The system delivered 25 µg phenylephrine every 30 s when systolic blood pressure was between 90% and 100% of baseline, or 2 mg ephedrine at this blood pressure range and heart rate < 60 beats.min(-1) ; and 50 µg phenylephrine or 4 mg ephedrine when systolic blood pressure was < 90% of baseline with the same heart rate criterion. Fifty-seven women received standardised spinal anaesthesia. Twenty-seven (47.4%) had at least one reading of hypotension defined as systolic blood pressure < 80% baseline. Systolic blood pressure was within 20% of the baseline in a mean (SD) of 79.8 (20.9)% of measurements. Fifty-three (93.0%) women required phenylephrine before delivery while 10 (17.5%) required ephedrine. Six women (10.5%) experienced nausea and three (5.3%) vomited. The system was able to achieve a low incidence of maternal hypotension with good maternal and fetal outcomes.

Hydrocortisone for Treatment of Hypotension in the Newborn.

Newborns, and especially premature newborns, are at significant risk for developing hypotension in the first week or two after birth. The etiology of hypotension in the newborn may vary, but the very low birth weight and extremely low birth weight preterm infants are less likely to respond to conventional cardiovascular support when they develop hypotension. This article reviews the least conventional treatment using hydrocortisone for hypotension that is refractory to conventional volume replacement and/or vasopressor medications with the underlying assumption that sick and premature newborns have a relative or measured adrenal insufficiency. The addition of hydrocortisone in the treatment of hypotension in the newborn is becoming more common but is not universally advocated. However, the supportive evidence is growing, and, as reviewed, use of hydrocortisone requires judicious and cautious regard.

Effectiveness of Rosmarinus officinalis essential oil as antihypotensive agent in primary hypotensive patients and its influence on health-related quality of life.

ETHNOPHARMACOLOGICAL RELEVANCE: To study Rosmarinus officinalis (Rosemary) essential oil effect on primary hypotension and its influence on both physical and psychological aspects responsible for health-related quality of life (HRQOL) of patients. METHODOLOGY: Thirty-two patients with diagnosed hypotension were recruited between March 2007 and September 2008 for a prospective study for 72 weeks in a Spanish pharmacy. Clinical evaluation was carried out through the control of systolic and diastolic blood pressure levels (SBP and DBP, respectively) according to the International Standards from the American Society of Hypertension. HRQOL data were recorded within the SF-36 Health Survey(®) questionnaire throughout the study. Statistical methods were used as the essential tools to evaluate the effectiveness of Rosemary essential oil and to assess the relationship between the two quantitative variables (SBP and DBP) and scores from physical and mental summary components (PSC and MSC) obtained from the SF-36 Health Survey. RESULTS: Both blood pressure variables of SBP and DBP reflect the clinically significant antihypotensive effect of Rosemary essential oil that was maintained throughout the treatment period. After validation of the use of the questionnaire (Cronbach's alpha coefficient>0.82), statistically significant differences have been found between pre-treatment and post-treatment values of PSC and MSC, which indicate an improvement in these parameters that is directly related to the variation in blood pressure values. CONCLUSIONS: The increase achieved in blood pressure values after administration of Rosemary essential oil is clinically significant. The results obtained from this prospective clinical trial prove the effectiveness of statistical methodology as a new approach to explain the antihypotensive effect of rosemary essential oil and its relationship with the improvement in patients' quality of life.

Assessment of the plethysmographic variability index as a predictor of fluid responsiveness in critically ill patients: a pilot study.

Optimising intravascular volume in patients with hypotension requiring vasopressor support is a key challenge of critical care medicine. The optimal haemodynamic parameter to assess fluid responsiveness in critically ill patients, particularly those requiring a noradrenaline infusion and mechanical ventilation, remains uncertain. This pilot study assessed the accuracy of the plethysmographic variability index (PVI), (Radical-7 pulse co-oximeter, Masimo®, Irvine, CA, USA) in predicting fluid responsiveness in 25 patients who required noradrenaline infusion to maintain mean arterial pressure over 65 mmHg and were mechanically ventilated with a 'lung-protective' strategy, and whether administering a fluid bolus was associated with a change in PVI (Δ PVI). In this study, fluid responsiveness was defined as an increase in stroke volume of greater than 15% after a 500 ml bolus of colloid infusion over 20 minutes. Of the 25 patients included in the study, only 12 (48%) were considered fluid responders. As static haemodynamic parameters, PVI, central venous pressure and inferior vena cava distensibility index were all inaccurate at predicting volume responsiveness with PVI being the least accurate (area under the receiver operating characteristic curve=0.41, 95% confidence interval 0.18 to 0.65). However, fluid responsiveness was associated with a change in PVI, but not a change in heart rate or central venous pressure. This association between Δ PVI and fluid responsiveness may be a surrogate marker of improved cardiac output following a fluid bolus and warrants further investigation.

[Use of ephedrine prefilled syringes reduces anesthesia costs]. / Réduction des coûts grâce à l'utilisation des seringues préremplies d'éphédrine.

OBJECTIVE: The aim of the present study was to compare the consumption and cost of ephedrine in parturients with respect to two packagings: ampoules and prefilled syringes. STUDY DESIGN: Prospective observational study in a French university obstetrical unit. PATIENTS AND METHODS: Assessing the consumption and cost of ephedrine during two consecutive periods of 14 days: use of ampoules for period 1 (P1) versus use of prefilled syringes for period 2 (P2). Consumption was daily evaluated. The costs (ampoules and consumable supplies for P1 and prefilled syringes for P2) were calculated on the basis of the price list given by our institutional pharmacy. The number of parturients and the anaesthetic techniques which were performed were prospectively recorded. RESULTS: One hundred and thirteen parturients were managed for the present study. The number of parturients and the anaesthetic care were similar between the two periods. In contrast, 155 ampoules were used for P1 versus 45 prefilled syringes for P2 (p<0.0001). The cost per parturient was 3.1 euro for P1 versus 2.6 euro for P2, i.e. 0.5 euro was saved for each parturient. CONCLUSION: The results of the present study show that the use of prefilled syringes reduces significantly the wastage of ephedrine, allowing subsequent cost minimization in obstetrical anaesthesia.

Controlling hypertension and hypotension immediately post stroke (CHHIPS)--a randomised controlled trial.

OBJECTIVES: To assess the effects of acute pressor and depressor blood pressure (BP) manipulation on 2-week death and dependency following acute stroke and investigate the safety and efficacy of such treatments. DESIGN: A multicentre, prospective, randomised, double-blind, placebo-controlled titrated-dose trial. SETTING: Five hospitals in England. PARTICIPANTS: Patients over 18 years admitted to hospital with a clinical diagnosis of suspected stroke and either (1) symptom onset < 36 hours and hypertension, defined as systolic BP (SBP) < 160 mmHg (depressor arm), or (2) symptom onset < 12 hours and hypotension, defined as SBP < or = 140 mmHg (pressor arm). INTERVENTIONS: Patients were allocated to either the pressor or the depressor arm depending on blood pressure at randomisation. The ratio of allocation to active intervention versus matched placebo was 2:1 for the depressor arm and 1:1 for the pressor arm. MAIN OUTCOME MEASURES: The primary end point was death and dependency at 2 weeks, with dependency defined as a modified Rankin score < 3. Secondary end points were the safety of acute pressor (0-12 hours post stroke) and depressor (0-36 hours post stroke) BP manipulation in stroke patients; whether effects of BP reduction are influenced by stroke type (ischaemic versus haemorrhagic); whether alternative routes for administration of antihypertensive therapy (including sublingual and intravenous) are effective in dysphagic stroke patients; whether effects of BP manipulation are influenced by the time to treatment; and the short- and medium-term cost-effectiveness of such therapy in the acute post-stroke period on subsequent disability or death. RESULTS: 180 patients were recruited over the 36-month trial period, 179 in the depressor arm and one in the pressor arm (who received placebo). No significant difference was found in death or dependency at 2 weeks between those receiving active depressor treatment with lisinopril or labetalol and those receiving placebo, although numbers recruited to the trial were lower than projected. Active treatment was not associated with an increase in early neurological deterioration despite significantly greater reductions in BP at 24 hours and 2 weeks with active therapy compared with placebo. Active treatment was generally well tolerated and treatment discontinuation rates were similar in active and placebo groups. Survival analysis showed that the active treatment group had a lower mortality at 3 months than the placebo group (p = 0.05). The pressor arm was closed early because of problems with recruitment, so no conclusions can be drawn regarding this therapy. CONCLUSIONS: Oral and sublingual lisinopril and oral and intravenous labetalol are effective BP-lowering agents in acute cerebral infarction and haemorrhage and do not increase the likelihood of early neurological deterioration. The study was not sufficiently powered to detect a difference in disability or death at 2 weeks. However, the 3-month difference in mortality in favour of active treatment is of interest, although care must be taken in interpretation of the results. Further work is needed to confirm this and to assess whether there are differences in the effectiveness of labetalol compared with lisinopril in terms of reducing death or dependency after acute stroke, and whether the introduction of treatment post stroke earlier than was achieved here would be of greater benefit.

Oral midodrine is effective for the treatment of hypotension associated with carotid artery stenting.

Hypotension is commonly encountered during carotid artery stenting (CAS), mediated by vagal stimulation and suppression of sympathetic outflow. Some patients require treatment with intravenous vasopressors (dopamine, nor-epinephrine, or phenylephrine). The authors describe the successful use of the oral agent midodrine as an alternative to intravenous vasopressors in the treatment of hypotension related to CAS. Of 55 patients who underwent elective CAS, 19 (35%) experienced significant hypotension, and 15 (27%) required vasopressor therapy. Eleven patients received intravenous dopamine infusion in an intensive care setting, whereas 4 received oral midodrine in a regular telemetry unit. All patients eventually recovered and were discharged without any residual cardiovascular or neurological complications. No major side effects were noted with the use of both dopamine and midodrine. Cost of hospitalization was significantly higher in the dopamine group because of the need for ICU admission.

Evaluation of relationship between arterial and venous blood gas values in the patients with tricyclic antidepressant poisoning.

INTRODUCTION: Determination of arterial blood gas (ABG) values is essential in the evaluation of patients with TCA poisoning. The relationship between arterial and venous blood gas pH has not been established in TCA poisoning. In TCA poisoning, blood vessels vasodilatation due to antidepressant-induced alpha-blockade and also metabolic acidosis may lead to arterialization of venous blood, which in turn enhances the relationship between ABG and VBG parameters. Therefore this study was designed to evaluate the relationship between ABG and VBG pH values in TCA poisoned patients. METHODS: This prospective study was performed in the Poisoning Emergency Department of Noor Hospital, Isfahan, Iran. Samples for arterial and venous blood gas analysis were obtained during initial evaluation of TCA-poisoned patients and 30 min after treatment with sodium bicarbonate. The venous blood gas samples were collected with samples for other blood tests at the time of intravenous line insertion. Laboratory data were recorded on a database form initiated in the emergency department and analyzed by paired student t-test. The degree of agreement between the arterial and venous pH measurements was evaluated by Bland and Altman method. RESULTS: Data from 50 TCA-poisoned patients were analyzed. There were significant differences between mean differences of ABG and VBG parameter values on the initial evaluation. There was also a relationship between arterial and venous pH on the initial evaluation. CONCLUSION: In TCA poisoning, the peripheral venous pH measurement is a valid and reliable substitute for arterial pH.

Desarrollo de un medicamento para el tratamiento de la hipotensión arterial y la operación de la catarata / Development of a drug for treating arterial hypotension and cataract surgery

Se desarrolló una formulación de clorhidrato de fenilefrina inyectable para el tratamiento de la hipotensión arterial y la cirugía oftalmológica, para lo cual se diseñaron y estudiaron 3 formulaciones; se selecció la más factible para la continuidad del estudio. El ensayo de estabilidad del producto a diferentes temperaturas durante 222 días y en estante por un período de 24 meses, se realizó mediante la aplicación del análisis de cromatografía líquida de alta resolución. La formulación obtenida se comparó desde el punto de vista farmacológico y toxicológico con un producto comercial. Los resultados demostraron que la formulación desarrollada cumple con los ensayos de estabilidad y tiene una potencia farmacológica en relación con el comercial del 113 por ciento; no existieron diferencias entre la actividad de los 2 productos comparados. El comercial resultó más tóxico que la formulación desarrollada al tener una DL50 superior. El producto logrado con el desarrollo tecnológico empleado cumple con las especificaciones de calidad de la USP 26

[Pharmacotherapy of arterial hypertension and pharmacoeconomic aspects of hypotensive therapy in elderly patients in Poland]. / Leczenie farmakologiczne nadcisnienia tetniczego oraz wybrane aspekty farmakoekonomiczne terapii hipotensyjnej u chorych w starszym wieku w Polsce.

The aim of our study was to examine the use of pharmacological therapy and to evaluate the economical aspects of treating hypertension (HT) in elderly patients in Poland. Two hundred and sixty eight elderly persons (147 females, 121 males; mean age: 72.2 +/- 6.0 years) were selected from Polish population by stratified and cluster random sampling with quotas. BP measurement was performed 3 times every 2 minutes at respondents home. In the questionnaire, awareness of HT was assessed. Prevalence of hypertension among subjects aged 65 years and over by JNC VI criteria (SAP > or = 140 mm Hg, DAP > or = 90 mm Hg or hypotensive therapy) was 74%. Awareness of HT was equal to 61%. Eleven percent of all hypertensives were well controlled. Among hypertensives, 71% took prescribed antihypertensive drugs on a regular basis. Patients with HT were taking the following antihypertensive drugs: diuretics 16%, diuretics and reserpine 20%, beta-blockers 19%, ACE inhibitors 53%, calcium antagonists 30%, and other 3%. Newer drugs were prescribed in 7%, and multi-source (generic) products in 93%. The average cost of treatment with one drug was 147 PLN (37.5 USD) per year (newer drugs: 413 PLN; multi-source product 126 PLN). Assuming those data and number of elderly people in Poland (4.335 mln), we estimated that 3.208 mln of subjects have had hypertension according to JNC VI criteria. Only 1.957 mln of patients with HT have been detected and only 0.353 mln of hypertensives have been well controlled. The approximate global cost of antihypertensive drugs per year in elderly patients in Poland has been equal to 285 mln PLN (72.8 mln USD). In hypothetical situation with optimal (100%) detection and control of HT the global cost by the actual rate of regularity in taking drugs would increase to 569 mln PLN (145.3 mln USD). The prevalence of HT in elderly people in Poland is very high. In elderly hypertensives ACE inhibitors are used most often. More than 90% of prescribed drugs are multi-source products. An optimal improvement of HT detection and control would cause a two-fold augmentation of the costs of pharmacological therapy.