Biological effects of acute pravastatin treatment in patients after aneurysmal subarachnoid hemorrhage: a double-blind, placebo-controlled trial

OBJECT: The authors previously demonstrated that acute pravastatin therapy in patients after aneurysmal subarachnoid hemorrhage (SAH) ameliorates vasospasm-related delayed ischemic neurological deficits. The object of this study was to continue to examine potential mechanisms of these beneficial effects. METHODS: Eighty patients with aneurysmal SAH (age range 18-84 years; time to onset 1.8 +/- 1.3 days) were enrolled in a double-blind study and randomized to receive 40 mg of oral pravastatin or placebo daily for as long as 14 days. Daily transcranial Doppler ultrasonography and blood tests every 3 days (including full blood cell counts, coagulation profiles, fasting glucose and lipid profiles, and serum biochemistry) were performed during the trial period. RESULTS. No significant differences were found in baseline laboratory data between the trial groups. Subsequent measurements during the 14-day trial showed reduced low-density lipoprotein (LDL) cholesterol levels and total/high-density lipoprotein cholesterol ratios between Days 3 and 15 (p < 0.05), and increased D-dimer levels (p < 0.05) on Day 6, in the pravastatin group. Patients who received pravastatin but developed vasospasm had significantly lower baseline LDL cholesterol levels or a less extensive reduction in LDL cholesterol levels (p < 0.05), and greater increases in plasma fibrinogen (p = 0.009) and serum C-reactive protein on Day 3 (p = 0.007), compared with those patients without vasospasm. The reduction in LDL cholesterol levels on Day 3 in the placebo group correlated with the duration of normal cerebral autoregulation on the ipsilateral side of the ruptured aneurysm (p = 0.002). CONCLUSIONS. In addition to functioning through a cholesterol-independent pathway, cerebrovascular protection from acute statin therapy following aneurysmal SAH may also function through cholesterol-dependent mechanisms.     

Magnesium sulfate in the management of patients with aneurysmal subarachnoid hemorrhage: a randomized, placebo-controlled, dose-adapted trial

BACKGROUND: Recent studies suggest that high-dose MgSO4 therapy is safe and reduces the incidence of DIND and subsequent poor outcome after SAH. We intended to assess the safety and efficacy of high-dose MgSO4 therapy after SAH as means to prevent DIND and to evaluate the impact on clinical outcome. METHODS: This was a prospective, randomized, single-blind, placebo-controlled study. The MgSO4 infusion was adjusted every 12 hours until day 12 according to the target serum Mg2+ level. The occurrence of DIND, secondary infarction, side effects, and the outcome after 3 and 12 months were assessed. RESULTS: Fifty-eight patients were randomized; 27 received placebo and 31 MgSO4. The difference in occurrence of DIND and secondary infarction was not significant. The intention-to-treat analysis revealed a trend toward better outcome (P = .083) after 3 months. On-treatment analysis showed a significantly better outcome after 3 months (P = .017) and a trend toward better outcome after 1 year (P = .083). Significantly more often hypotension (P = .040) and hypocalcemia (P = .005) occurred as side effects in the treatment group. In 16 patients (52%), the MgSO4 therapy had to be stopped before day 12 because of side effects. No predictive factor leading to termination was found in a postrandomization analysis. CONCLUSIONS: High-dose MgSO4 therapy might be efficient as a prophylactic adjacent therapy after SAH to reduce the risk for poor outcome. Nevertheless, because of the high frequency of the side effects, patients should be observed in an intensive or intermediate care setting.     

Effect of AT877 on cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Results of a prospective placebo-controlled double-blind trial.

With the cooperation of 60 neurosurgical centers in Japan, a prospective randomized placebo-controlled double-blind trial of a new calcium antagonist AT877 (hexahydro-1-(5-isoquinolinesulfonyl)-1H-1,4-diazepine hydrochloride, or fasudil hydrochloride) was undertaken to determine the drug's effect on delayed cerebral vasospasm in patients with a ruptured cerebral aneurysm. A total of 276 patients, who underwent surgery within 3 days after subarachnoid hemorrhage (SAH) of Hunt and Hess Grades I to IV, were entered into the study. Nine patients were excluded because of protocol violation. The remaining 267 patients received either 30 mg AT877 or a placebo (saline) by intravenous injection over 30 minutes, three times a day for 14 days following surgery. Demographic and clinical data were well matched between the two groups. It was found that AT877 reduced angiographically demonstrable vasospasm by 38% (from 61% in the placebo group to 38% in the AT877 group, p = 0.0023), low-density regions on computerized tomography associated with vasospasm by 58% (from 38% to 16%, p = 0.0013), and symptomatic vasospasm by 30% (from 50% to 35%, p = 0.0247). Furthermore, AT877 reduced the number of patients with a poor clinical outcome associated with vasospasm (moderate disability or worse on the Glasgow Outcome Scale at 1 month after SAH) by 54% (from 26% to 12%, p = 0.0152). There were no serious adverse events reported in the AT877 group. This is the first report of a placebo-controlled double-blind trial that has demonstrated a significant reduction in angiographically revealed vasospasm by intravenous drug therapy.     

Case-control study of clinical outcome after aneurysmal subarachnoid hemorrhage

The clinical and neuropathological features of 84 nonsurvivors of aneurysmal subarachnoid hemorrhage (consecutive autopsy series) were compared with those of 51 survivors (consecutive clinical series). The groups differed significantly in the type of bleeding: 58% of the nonsurvivors had massive subarachnoid hemorrhage (MSAH) compared to 10% of the survivors (P less than 0.00001); 54% of the nonsurvivors had intraventricular hemorrhage (IVH) compared to 29% of the survivors (P less than 0.008); 45% of the nonsurvivors had intracerebral hematoma (ICH) compared to 8% of the survivors (P less than 0.00001). Only 1 of the 19 patients with both MSAH and ICH survived. The incidence of cerebral infarction was similar in nonsurvivors (31%) and survivors (29%). In the absence of associated MSAH, IVH, or ICH, cerebral infarction was uncommon (11%). Documented in-hospital rebleeding was uncommon in nonsurvivors (13%) and survivors (2%). Admission neurological status did not predict outcome independent of the extent of the initial bleeding. Comparison of the two groups suggests that the type and extent of initial bleeding are the most important determinants of mortality in aneurysmal subarachnoid hemorrhage.     

Predictors of shunt dependency after aneurysmal subarachnoid hemorrhage: results of a single-center clinical trial

Background

Hydrocephalus (HC) after aneurysmal subarachnoid hemorrhage (aSAH) is a common sequel. Proper selection of patients in need of permanent cerebrospinal fluid (CSF) diversion is, however, not straightforward. The aim of this study was to identify predictors of CSF shunt dependency following aSAH.

Methods

We re-analyzed data acquired from aSAH patients previously enrolled in a prospective, controlled single-center clinical trial in which shunt dependency was not one of the end points. In the present study patients were allocated into two groups: those receiving a shunt (here denoted as shunt dependent) and those not receiving a shunt, based on a clinical decision process. Predictors of shunt dependency were identified by applying uni- and multivariable analysis. We tested a set of predefined possible risk factors based on the results of the clinical trial, including the impact of CSF drainage volume exceeding 1,500 ml during the 1st week after ictus.

Results

Ninety patients were included in the study. Significant predictors of shunt dependency were poor clinical grade at admission [odds ratio (OR) 4.7, 95 % confidence interval (CI) 1.2–18.4], large amounts of subarachnoid blood (OR 3.8, 95 % CI 1.0–14.0), large ventricular size on preoperative cerebral computer tomographic (CT) scans (OR 1.0, 95 % CI 1.0–1.1), and CSF volume drainage exceeding 1,500 ml during the 1st week after the ictus (OR 16.3, 95 % CI 4.0–67.1). Age ≥70 years, larger amounts of intraventricular blood, vertebrobasilar aneurysm, and endovascular treatment tended to increase the likelihood of receiving a shunt. Outcome was not significantly different between shunted and non-shunted patients.

Conclusions

In this cohort of patients with clinical grade aSAH at admission, larger amounts of subarachnoid blood and large ventricular size on preoperative cerebral CT, and CSF drainage in excess of 1,500 ml during the 1st week after the ictus were significant predictors of shunt dependency. Shunt dependency did not hamper outcome.     

Effects of different photobiomodulation dosimetries on temporomandibular dysfunction: a randomized,double-blind,placebo-controlled clinical trial

Changes involving temporomandibular joint, masticatory musculature, and associated structures characterize temporomandibular dysfunction (TMD). The analgesic and anti-inflammatory effect produced by photobiomodulation has contributed to pain relief and functional improvement. However, the parameters to be used have not yet been well established. The aim of this study is to compare the efficacy of three different photobiomodulation dosimetries in the treatment of patients with TMD. A randomized, double-blind, placebo-controlled clinical trial with 44 subjects divided into the groups 8 J/cm² (n?=?11), 60 J/cm² (n?=?11), 105 J/cm² (n?=?11), and control (n?=?11). Pain, symptom severity, and joint mobility were evaluated before and after a ten-session protocol of photobiomodulation with AlGaAs laser (830 nm), at a power density of 30 mW/cm². The mouth opening increased in the 8-J/cm² group from 10.49?±?4.68 to 15.40?±?6.43 degrees, and in the right protrusion from 9.80?±?4.2 to 12.56?±?5.40 degrees after the intervention protocol (p?<?0.05). All groups significantly decreased pain (p?<?0.05). 830-nm laser photobiomodulation was effective in reducing TMD pain and symptoms at all doses tested. Only the doses of 8 J/cm² were effective regarding maximal opening and protrusion of the mandible.     

Influence of aspirin on outcome following aneurysmal subarachnoid hemorrhage

OBJECT: Previous studies have indicated an increased incidence of death in patients with subarachnoid hemorrhage (SAH) who are currently receiving anticoagulation therapy. The significance of previous aspirin use in patients with SAH is unknown. The authors analyzed the effects of prior aspirin use on clinical course and outcomes following aneurysmal SAH. METHODS: The medical records of 305 patients with angiogram-confirmed aneurysmal SAH who consecutively presented to our institution between 1990 and 1997 within 7 days of ictus were analyzed. Twenty-nine (9.5%) of these patients had a history of regular aspirin use before onset of the SAH. The Glasgow Outcome Scale (GOS) was used to measure patient outcome at the longest available follow up. Aspirin users were older on average than nonusers (59 years of age compared with 53 years; p = 0.018). The mean admission Hunt and Hess grades of patients with and without aspirin use were similar (2 compared with 2.3; p = 0.51). Two trends, which did not reach statistical significance, were observed. 1) The rebleeding rate in aspirin users was 14.3%, compared with a 4.7% rebleeding rate in nonusers (p = 0.06). 2) Permanent disability from vasospasm was less common among aspirin users (23% compared with 50%; p = 0.069). Outcomes did not differ between aspirin users and nonusers (mean GOS Score 3.83 compared with GOS Score 3.86, respectively; p = 0.82). CONCLUSIONS: Despite trends indicating increased rebleeding rates and a lower incidence of permanent disability due to delayed ischemic neurological deficits, there was no significant effect of previous aspirin use on overall outcome following aneurysmal SAH. Based on these preliminary data, the presence of an intracranial aneurysm is not a strict contraindication to aspirin use.     

Preoperative dexamethasone improves surgical outcome after laparoscopic cholecystectomy: a randomized double-blind placebo-controlled trial

OBJECTIVE: To determine the effects of preoperative dexamethasone on surgical outcome after laparoscopic cholecystectomy (LC). SUMMARY BACKGROUND DATA: Pain and fatigue are dominating symptoms after LC and may prolong convalescence. METHODS: In a double-blind, placebo-controlled study, 88 patients were randomized to intravenous dexamethasone (8 mg) or placebo 90 minutes before LC. Patients received a similar standardized anesthetic, surgical, and multimodal analgesic treatment. All patients were recommended 2 days postoperative duration of convalescence. The primary endpoints were fatigue and pain. Preoperatively and at several times during the first 24 postoperative hours, we measured C-reactive protein (CRP) and pulmonary function, pain scores, nausea, and number of vomiting episodes were registered. Analgesic and antiemetic requirements were recorded. Also, on a daily basis, patients reported scores of fatigue and pain before and during the first postoperative week and the dates for resumption of work and recreational activities. RESULTS: Eight patients were excluded from the study, leaving 40 patients in each study group for analysis. There were no apparent side effects of the study drug. Dexamethasone significantly reduced postoperative levels of CRP (P = 0.01), fatigue (P = 0.01), overall pain, and incisional pain during the first 24 postoperative hours (P < 0.05) and total requirements of opioids (P < 0.05). In addition, cumulated overall and visceral pain scores during the first postoperative week were significantly reduced (P < 0.05). Dexamethasone also reduced nausea and vomiting on the day of operation (P < 0.05). Resumption of recreational activities was significantly faster in the dexamethasone group versus placebo group (median 1 day versus 2 days) (P < 0.05). CONCLUSION: Preoperative dexamethasone (8 mg) reduced pain, fatigue, nausea and vomiting, and duration of convalescence in patients undergoing noncomplicated LC, when compared with placebo, and is recommended for routine use.     

Prophylactic hyperdynamic postoperative fluid therapy after aneurysmal subarachnoid hemorrhage: a clinical, prospective, randomized, controlled study

OBJECTIVE: To investigate the role of prophylactic hyperdynamic postoperative fluid therapy in preventing delayed ischemic neurological deficits attributable to cerebral vasospasm. METHODS: We designed a prospected, randomized, controlled study and included 32 patients with subarachnoid hemorrhage. Sixteen patients received hypervolemic hypertensive hemodilution fluid therapy; the other 16 patients received normovolemic fluid therapy. All patients were monitored for at least 12 days, with clinical assessments, transcranial Doppler recordings, single-photon emission computed tomographic (SPECT) scanning, and routine computed tomographic scanning. For fluid balance monitoring, a number of blood samples were obtained on a daily basis and continuous central venous pressure and mean arterial blood pressure measurements were performed for both groups. All patients received intravenous nimodipine infusions between Day 1 and Day 12. End points of this study were clinical outcomes, clinically evident and transcranial Doppler sonography-evident vasospasm, SPECT findings, complications, and costs. Clinical examinations (using the Glasgow Outcome Scale) performed 1 year after discharge, together with neuropsychological assessments and SPECT scanning, were the basis for the evaluation of clinical outcomes. RESULTS: No differences were observed between the two groups with respect to cerebral vasospasm (as observed clinically or on transcranial Doppler recordings). When regional cerebral blood flow was evaluated by means of SPECT analysis performed on Day 12 after subarachnoid hemorrhage, no differences were revealed. One-year clinical follow-up assessments (with the Glasgow Outcome Scale), including SPECT findings and neuropsychological function results, did not demonstrate any significant group differences. Costs were higher and complications were more frequent for the hyperdynamic therapy group. CONCLUSION: Neither early nor late outcome measures revealed any significant differences between the two subarachnoid hemorrhage treatment models.     

Alpha-blockers impact stent-related symptoms: a randomized, double-blind, placebo-controlled trial

Abstract Background and Purpose: Ureteral stents are indispensable tools in endourology, although they often are associated with bothersome lower urinary tract symptoms. This study was conducted to evaluate the effect of alfuzosin on urinary symptoms, quality of life, and pain in patients after Double-J ureteral stent placement in a randomized, placebo-controlled trial. Patients and Methods: This study was conducted from July 2008 to May 2009. A total of 130 patients underwent placement of a Double-J stent after retrograde semirigid ureteroscopy for ureteral stones. They were randomized in two groups. Group 1 (n=65) received alfuzosin 10?mg once daily and group 2 (n=65) received placebo for 1 week. Both groups also received standardized analgesia. The stent symptoms were measured and recorded 1 week after the procedure. Statistical analyses were performed using the chi-square test and Student t test with P<0.05 considered significant. Results: The demographic profile including patient and stone-related parameters were comparable. Group 1 had significantly less urinary symptoms (P<0.05). The quality-of-life assessment was better in the alfuzosin arm than in the placebo arm (P<0.001). The mean pain score was 1.15 in group 1 and 3.89 in the placebo group (P<0.001). None of the patients in either of the arms withdrew from treatment; there were minimal adverse effects in the treatment arm. The limitation of the current work includes relatively smaller sample size and use of single type of stent. Conclusions: Alfuzosin 10?mg once daily in patients with a Double-J stent significantly decreases the bothersome urinary symptoms, besides decreasing significantly the pain associated with the stent.     

Cocaine use as a predictor of outcome in aneurysmal subarachnoid hemorrhage

OBJECT: The goal of this study was to analyze the relationship between cocaine use and outcomes of aneurysmal subarachnoid hemorrhage (SAH). METHODS: A retrospective review was performed of the medical records of patients with intracranial aneurysms treated at a single institution between January 1996 and December 2001. Only patients who presented with SAH were included in the study. The covariates chosen for the statistical analysis included the following: patient age, sex, and race; systolic and mean arterial blood pressure measurements on hospital admission; Hunt and Hess and Fisher grades; pre-existent major systemic disease; and history of alcohol, tobacco, or cocaine use. The Glasgow Outcome Scale (GOS) was used to standardize outcome and was dichotomized such that a score between 1 and 3 was considered a poor outcome and a score of 4 or 5 was considered a favorable outcome. The records of 151 patients were reviewed and 108 of these presented with aneurysmal SAH. Of these 108 patients, 36 (33.3%) had used cocaine within 24 hours before presentation. A Hunt and Hess grade of IV or V was assigned to 20 (55.6%) of 36 patients who used cocaine, compared with eight (11.1%) of 72 patients who did not; this difference was found to be statistically significant (p < 0.0001). Twenty-eight patients (77.8%) in the cocaine user group and 20 patients (27.8%) in the non-cocaine user group experienced clinically significant, angiographically confirmed vasospasm during their hospital course (p < 0.0001). Cocaine use was associated with a 2.8-fold greater risk of developing vasospasm (95% confidence interval [CI] 1.86-4.22). A GOS score of 1, 2, or 3 was assigned to 33 patients (91.7%) in the cocaine user group and to 20 patients (27.8%) in the non-cocaine user group (p < 0.0001). Cocaine use was associated with a 3.3-fold greater risk of poor outcome (95% CI 2.24-4.85). This association was found to be independent of Hunt and Hess grade as well as of vasospasm. CONCLUSIONS: Cocaine adversely affects both the presentation of and outcome in patients with aneurysmal SAH who are undergoing treatment for this disease. The vasoactive properties of the drug appear to aggravate the already tenuous situation of SAH and increase both the occurrence and influence of cerebral vasospasm. Statistical analysis demonstrates that cocaine directly affects both presentation and outcome in a significant manner. It is the authors' interpretation of the results of this retrospective review that cocaine use negatively affects outcome to such an extent that it should be considered equal to the presence of a major systemic illness when determining Hunt and Hess grade.     

Recombinant coagulation factor VIIa in major liver resection: a randomized, placebo-controlled, double-blind clinical trial

BACKGROUND: Prevention of bleeding episodes in noncirrhotic patients undergoing partial hepatectomy remains unsatisfactory in spite of improved surgical techniques. The authors conducted a randomized, placebo-controlled, double-blind trial to evaluate the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in major partial hepatectomy. METHODS: Two hundred four noncirrhotic patients were equally randomized to receive either 20 or 80 microg/kg rFVIIa or placebo. Partial hepatectomy was performed according to local practice at the participating centers. Patients were monitored for 7 days after surgery. Key efficacy parameters were perioperative erythrocyte requirements (using hematocrit as the transfusion trigger) and blood loss. Safety assessments included monitoring of coagulation-related parameters and Doppler examination of hepatic vessels and lower extremities. RESULTS: The proportion of patients who required perioperative red blood cell transfusion (the primary endpoint) was 37% (23 of 63) in the placebo group, 41% (26 of 63) in the 20-microg/kg group, and 25% (15 of 59) in the 80-microg/kg dose group (logistic regression model; P = 0.09). Mean erythrocyte requirements for patients receiving erythrocytes were 1,024 ml with placebo, 1,354 ml with 20 microg/kg rFVIIa, and 1,036 ml with 80 microg/kg rFVIIa (P = 0.78). Mean intraoperative blood loss was 1,422 ml with placebo, 1,372 ml with 20 microg/kg rFVIIa, and 1,073 ml with 80 microg/kg rFVIIa (P = 0.07). The reduction in hematocrit during surgery was smallest in the 80-microg/kg group, with a significant overall effect of treatment (P = 0.04). CONCLUSIONS: Recombinant factor VIIa dosing did not result in a statistically significant reduction in either the number of patients transfused or the volume of blood products administered. No safety issues were identified.     

Poor-grade aneurysmal subarachnoid hemorrhage: relationship of cerebral metabolism to outcome

OBJECT: The majority of patients with poor-grade subarachnoid hemorrhage (SAH), that is, World Federation of Neurosurgical Societies (WFNS) Grades IV and V, have high morbidity and mortality rates. The objective of this study was to investigate cerebral metabolism in patients with low- compared with high-grade SAH by using bedside microdialysis and to evaluate whether microdialysis parameters are of prognostic value for outcome in SAH. METHODS: A prospective investigation was conducted in 149 patients with SAH (mean age 50.9 +/- 12.9 years); these patients were studied for 162 +/- 84 hours (mean +/- standard deviation). Lesions were classified as low-grade SAH (WFNS Grades I-III, 89 patients) and high-grade SAH (WFNS Grade IV or V, 60 patients). After approval by the local ethics committee and consent from the patient or next of kin, a microdialysis catheter was inserted into the vascular territory of the aneurysm after clip placement. The microdialysates were analyzed hourly for extracellular glucose, lactate, lactate/pyruvate (L/P) ratio, glutamate, and glycerol. The 6- and 12-month outcomes according to the Glasgow Outcome Scale and functional disability according to the modified Rankin Scale were assessed. In patients with high-grade SAH, cerebral metabolism was severely deranged compared with those who suffered low-grade SAH, with high levels (p < 0.05) of lactate, a high L/P ratio, high levels of glycerol, and, although not significant, of glutamate. Univariate analysis revealed a relationship among hyperglycemia on admission, Fisher grade, and 12-month outcome (p < 0.005). In a multivariate regression analysis performed in 131 patients, the authors identified four independent predictors of poor outcome at 12 months, in the following order of significance: WFNS grade, patient age, L/P ratio, and glutamate (p < 0.03). CONCLUSIONS: Microdialysis parameters reflected the severity of SAH. The L/P ratio was the best metabolic independent prognostic marker of 12-month outcome. A better understanding of the causes of deranged cerebral metabolism may allow the discovery of therapeutic options to improve the prognosis, especially in patients with high-grade SAH, in the future.     

The effect of solifenacin on postvoid dribbling in women: results of a randomized,double-blind placebo-controlled trial

Introduction and hypothesis

To determine the effectiveness of the muscarinic receptor antagonist solifenacin (VESIcare®) in the treatment of postvoid dribbling (PVD).

Methods

We carried out a multicenter, 12-week, double-blind, randomized, placebo-controlled, parallel design study. Between 2012 and 2015, a total of 118 women (age 18–89 years) with PVD at least twice/weekly, were randomized to receive solifenacin (5 mg; n?=?58) or placebo (n?=?60) once daily. The primary outcome was the percentage reduction in PVD episodes. Secondary outcomes included the percentage of patients with ≥50% reduction in PVD episodes and changes in quality of life.

Results

There were no differences in either the primary or secondary outcome variables. Subgroup analysis, based on those with more severe disease (>10 PVD episodes/week), showed a greater and significant percentage reduction in the frequency of PVD episodes per day (60.3% vs 32.1%; p =?0.035) and a higher percentage of patients showing ≥50% reduction in the frequency of PVD episodes with solifenacin (68.1% vs 45.8%; p =?0.0476). A significant solifenacin effect occurred at week 2 and continued through week 12 for the subgroup. For solifenacin, PVD reduction was the same for the entire cohort and subgroup, whereas for placebo, it was 10% lower in the subgroup, declining from 42% to 32%.

Conclusion

There were no differences in PVD outcomes between the solifenacin and placebo groups. Solifenacin may play a role in treating women with the most severe symptoms. Because of the powerful placebo response seen in this study, behavior-based interventions may be useful for treating PVD.

     

Cardioprotective effects of carnitine in extensive aortocoronary bypass grafting: a double-blind, randomized, placebo-controlled clinical trial

The cardioprotective effects of carnitine were tested in patients undergoing multiple aortocoronary bypass grafting. Intermittent aortic cross-clamping at 28 degrees C was used. Mean total cross-clamping time was 30 +/- 11 min. Patients were randomized into three groups: a control group receiving placebo (group 1), a group pretreated with 3 g carnitine intravenously before cardiopulmonary bypass (CPB) (group 2), and a group pretreated with 6 g carnitine intravenously (group 3). The markers of myocardial ischemia included levels of adenosine triphosphate, its catabolites, and creatine phosphate in transmural left ventricular biopsy specimens taken at the beginning and end of CPB, as well as hemodynamic recovery during weaning from CPB and for the next 24 h. The intravenous infusion of carnitine (3 or 6 g) had no hemodynamic effect. At the end of CPB myocardial tissue levels of adenosine triphosphate and creatine phosphate did not differ significantly among the groups (P greater than 0.05). Recovery of cardiac function during weaning from CPB and for the following 24 h was similar in all three groups (P greater than 0.05). It is concluded that pretreatment with carnitine neither facilitates weaning from cardiopulmonary bypass in patients undergoing aortocoronary bypass surgery nor favorably affects hemodynamic function during the next 24 h.     

Intravenous magnesium sulfate after aneurysmal subarachnoid hemorrhage: a prospective randomized pilot study

We performed a randomized, double-blind, pilot study on magnesium sulfate (MgSO4) infusion for aneurysmal subarachnoid hemorrhage (SAH).Sixty patients with SAH were randomly allocated to receive either MgSO4 80 mmol/day or saline infusion for 14 days. Patients also received intravenous nimodipine. Episodes of vasospasm were treated with hypertensive and hypervolemic therapy. Neurologic status was assessed 6 months after hemorrhage using the Barthel index and Glasgow Outcome Scale. Incidences of cardiac and pulmonary complications were also recorded.Patient characteristics, severity of SAH, and surgical treatment did not differ between groups. The incidence of symptomatic vasospasm decreased from 43% in the saline group to 23% in patients receiving MgSO4 infusion, but it did not reach statistical significance, P=0.06. For patients who had transcranial Doppler-detected vasospasm, defined as mean flow velocity >120 cm/s and a Lindegaard index >3, the duration was shorter in the magnesium group compared with controls (P<0.01). There was, however, no difference between groups in functional recovery or Glasgow Outcome Scale score. The incidence of adverse events such as brain swelling, hydrocephalus, and nosocomial infection was also similar in patients receiving MgSO4 or saline.In this small pilot study, MgSO4 infusion for aneurysmal SAH is feasible. On the basis of the preliminary data, a larger study recruiting approximately 800 patients is required to test for a possible neuroprotective effect of magnesium after SAH.     

Homeopathic treatment of mild traumatic brain injury: A randomized, double-blind, placebo-controlled clinical trial

BACKGROUND: Mild traumatic brain injury (MTBI) affects 750,000 persons in the United States annually. Five to fifteen percent have persistent dysfunction and disability. No effective, standard pharmacological treatment exists specifically for this problem. We designed a pilot research project to study the clinical effectiveness of homeopathic medicine in the treatment of persistent MTBI. METHOD: A randomized, double-blind, placebo-controlled trial of 60 patients, with a four-month follow-up (N = 50), was conducted at Spaulding Rehabilitation Hospital (SRH). Patients with persistent MTBI (mean 2.93 years since injury, SD 3.1) were randomly assigned to receive a homeopathic medicine or placebo. The primary outcome measure was the subject-rated SRH-MBTI Functional Assessment, composed of three subtests: a Difficulty with Situations Scale (DSS), a Symptom Rating Scale (SRS), and a Participation in Daily Activities Scale (PDAS). The SRH Cognitive-Linguistic Test Battery was used as the secondary measure. RESULTS: Analysis of covariance demonstrated that the homeopathic treatment was the only significant or near-significant predictor of improvement on DSS subtests (P =.009; 95% CI -.895 to -.15), SRS (P =.058; 95% CI -.548 to.01) and the Ten Most Common Symptoms of MTBI (P =.027; 95% CI -.766 to -.048). These results indicate a significant improvement from the homeopathic treatment versus the control and translate into clinically significant outcomes. CONCLUSIONS: This study suggests that homeopathy may have a role in treating persistent MTBI. Our findings require large-scale, independent replication.