Hypomagnesemia is common following cardiac surgery

Hypomagnesemia is a common disorder in noncardiac surgical patients in the postoperative period, but the effect of cardiac surgery on serum magnesium concentrations remains unclear. The authors hypothesized that cardiac surgery is associated with hypomagnesemia, and prospectively studied 101 subjects (60 +/- 13.1 years of age) undergoing coronary artery revascularization (n = 70), valve replacement (n = 24), or both simultaneously (n = 7). Blood samples and clinical biochemical data were collected before induction of anesthesia, prior to cardiopulmonary bypass (CPB), immediately after CPB, and on postoperative day 1. Blood samples were analyzed for ultrafilterable magnesium, total magnesium, ionized calcium, parathyroid hormone, and free fatty acid concentrations. Outcome variables were also determined. Eighteen of 99 (18.2%) subjects had hypomagnesemia preinduction and this number increased to 71 of 100 (71.0%) following cessation of CPB (P less than 0.05). Patients with postoperative hypomagnesemia had a higher frequency of atrial dysrhythmias (22 of 71 [31.0%] v 3 of 29 [10.3%], P less than 0.05) and required prolonged mechanical ventilatory support (22 of 63 [34.9%] v 4 of 33 [12.1%], P less than 0.05). Hypomagnesemia is common following cardiac surgical procedures with CPB and is associated with clinically important postoperative morbidity.     

Association of serum magnesium with cardiovascular mortality and all-cause mortality in peritoneal dialysis patients

Objective To investigate the association of serum magnesium with cardiovascular disease (CVD) and all-cause mortality in peritoneal dialysis patients. Methods A retrospective study was performed in patients who initiated peritoneal dialysis from January 1, 2013 to July 31, 2019 in the Shaoxing People's Hospital. According to the standard of serum magnesium, the patients were divided into control group (Mg≥0.7 mmol/L) and low-magnesium group (Mg﹤0.7 mmol/L). The differences in baseline biochemical variables, comorbidities, medications, and clinical outcomes between the two groups were compared. Logistic regression was used to analyze the related factors of hypomagnesemia. Kaplan-Meier survival analysis and Fine-Gray model were used to compare the difference in cumulative survival rate between the two groups. Cox regression model and competitive risk model were used to analyze the risk factors of all-cause mortality and CVD mortality. Results A total of 381 peritoneal dialysis patients were enrolled in this study. Among them, 321 patients were in control group and 60 patients in low-magnesium group. The total median follow-up time was 27(15, 43) months. There were significant differences in serum albumin, magnesium, phosphorus, intact parathyroid hormone, low-density lipoprotein chloesterol, high sensitivity C-reactive protein and 4-hour dialysate-to-plasma creatinine (4 h D/Pcr) between the two groups. CVD was the main cause of death in patients on peritoneal dialysis. Multivariate logistic regression analysis showed that hypoalbuminemia (OR=0.901, 95%CI 0.831-0.976, P=0.011), hypophosphatemia (OR=0.217, 95%CI 0.080-0.591, P=0.003), higher hsCRP (OR=1.276, 95%CI 1.066-1.528, P=0.008), and higher 4 h D/Pcr (OR=1.395, 95%CI 1.014-1.919, P=0.041) were independent risk factors for patients with hypomagnesemia. Kaplan-Meier survival curve analysis showed the cumulative survival rate of patients in low-magnesium group was significantly lower than that of control group (Log-rank χ2=5.388, P=0.020). Fine-Gray model analysis showed the cumulative CVD survival rate of low-magnesium group was significantly lower than that of control group (Gray=6.915, P=0.009). Multivariate-corrected Cox regression model and competitive risk model analysis showed that higher serum magnesium level was a protective factor for all-cause mortality and CVD mortality when serum magnesium was used as a continuous variable (HR=0.137, 95%CI 0.020-0.946, P=0.044; SHR=0.037, 95%CI 0.002-0.636, P=0.023, respectively). Hypomagnesemia was an independent risk factor for all-cause mortality and CVD mortality when serum magnesium was used as categorical variable (HR=1.864, 95%CI 1.044-3.328, P=0.035; SHR=2.117, 95%CI 1.147-3.679, P=0.029, respectively). Conclusions Hypomagnesemia is susceptible to peritoneal dialysis patients with hypoalbuminemia, hypophosphatemia, higher hsCRP and higher peritoneal transport characteristics. Hypomagnesemia is an independent risk factor for CVD mortality and all-cause mortality in peritoneal dialysis patients.     

ECG abnormalities in predicting secondary cerebral ischemia after subarachnoid haemorrhage

Summary Background. Electrocardiographic (ECG) abnormalities frequently occur after subarachnoid haemorrhage (SAH), and have been linked with poor outcome. The pathogenesis behind this relation is unclear. We hypothesized that cardiac dysfunction may contribute to the development of delayed cerebral ischemia (DCI) and investigated if electrocardiographic repolarization abnormalities on admission, representing this cardiac dysfunction, are related to DCI. We also assessed the additional value of ECG characteristics to establish prognosticators for clinical outcome (WFNS, age and Hijdra score). Method. In a series of 121 consecutive patients with aneurysmal SAH we related individual repolarization-like ECG changes (ST and T-wave changes, QTc prolongation, a U-wave) to the occurrence of DCI by means of Cox proportional hazard modelling and to poor outcome (death or dependence) with logistic regression analysis. We used ROC curves to assess the additional prognostic value of the most important ECG characteristics to established prognosticators. Findings. Only ST segment depression had a statistically significant relationship with the occurrence of DCI (HR 2.4 [95%CI 1.2–4.9]) in univariate analysis. In a similar analysis ST-elevation (OR 4.9; [95%CI 0.99–24.0]), ST-depression (OR 10.6; [95%CI 2.3–48.8]), T-wave inversion (OR 2.5; [95%CI 1.1–5.5]) and ischemic like ECG abnormalities (OR 8.3; [95%CI 3.0–22.2]) were significantly related to poor outcome. In multivariate models with extension of these ECG characteristics for establishing prognosticators the AUC of the ROC improved from 0.81 to 0.84. Conclusions. ECG abnormalities did not contribute to the prediction of DCI and have limited value in prognosticating poor outcome. The occurrence of DCI is not the explanation of this relationship between ECG characteristics and outcome.     

Outcome prediction with serum intercellular adhesion molecule-1 levels after aneurysmal subarachnoid hemorrhage.

OBJECT: Although upregulated adhesion molecule expression has been demonstrated in experimental models of subarachnoid hemorrhage (SAH) and in the cerebrospinal fluid of patients with aneurysmal SAH, the clinical significance of these proinflammatory findings remains unclear. The authors hypothesize that 1) serum levels of soluble intercellular adhesion molecule-l (ICAM-1) are increased in all patients with aneurysmal SAH shortly after the hemorrhagic event, and 2) elevated soluble ICAM-1 values are associated with poor patient outcome, even when controlling for the severity of the initial hemorrhagic insult. METHODS: One hundred one patients were prospectively enrolled and stratified according to their admission Hunt and Hess grade and functional status at discharge (modified Rankin Scale [mRS] score). Soluble ICAM-1 levels were determined every other day for 12 days post-SAH by using the enzyme-linked immunosorbent assay. Early soluble ICAM-1 levels (post-SAH Days 2-4) were increased compared with levels in control patients without SAH (p < 0.05). Patients with aneurysmal SAH who had a poor outcome (mRS Grades 4-6) had significantly higher soluble ICAM-1 levels over the first 2 weeks post-SAH compared with patients who had a good outcome (mRS Grades 0-3, p < 0.01). This association with outcome was predicted by late increases (Day 6, p = 0.07; Days 8-12, p < 0.05) rather than early increases (p = not significant) and was best seen in patients with Hunt and Hess Grades I and II. in whom only those with poor outcomes demonstrated delayed ICAM-1 elevations (p < 0.05). CONCLUSIONS: These data demonstrate a correlation between soluble ICAM-1 levels and functional outcome following aneurysmal SAH that appears to be, at least in part, independent of the initial hemorrhage.     

Allogeneic activation is attenuated in a model of mouse lung perfused with magnesium-deficient blood

Hypomagnesemia, which is frequently observed in patients treated with calcineurin inhibitors to prevent rejection after allogeneic transplantation, has been associated with a faster rate of decline in allograft function. The effect of hypomagnesemia on lung allograft has not been reported yet. In our model of isolated mouse lung, we have evaluated the early effects of allogeneic lung perfusion with blood from magnesium (Mg)-deficient mice for 3 h on lung activation and remodelling, compared to isogeneic perfusion. Hypomagnesemia (0.21+/-0.07 mmol Mg(2+)/l) was observed in blood from Mg-deficient mice, but no inflammatory pattern. The mRNA level of the intercellular adhesion molecule (ICAM)-1, but neither of the vascular cell adhesion molecule (VCAM)-1, nor of the cytokines tumor necrosis factor (TNF)alpha and interleukin (IL)-2, was enhanced (p<0.05). Although caspase-3 mRNA was transiently enhanced, no apoptotic cells were evidenced in lung tissues even after 3 h. Using cDNA array, we found that the genes encoding RANKL, RANK, TNFR2, NFATX, IL-1R2, IL-6R gp130, SOCS3, PDGFRB, P63, CSF3R, CXCL1, CXCL5, CX3CL1, CSF1, which are involved in inflammation and apoptosis regulation, were markedly up-regulated in allogeneic conditions. Our results support a limited allogeneic activation and an early stage of the inflammatory process in lung, at the time of inflammatory cell recruitment without lung tissue remodelling, as a result of hypomagnesemia. These findings suggest that cyclosporine-related hypomagnesemia, observed in most of the transplanted patients, does not constitute an additional risk for lung allograft outcome.     

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.     

Whole blood ionized magnesium: age-related differences in normal values and clinical implications of ionized hypomagnesemia in patients undergoing surgery for congenital cardiac disease

OBJECTIVES: We sought to (1) determine reference values for whole blood ionized magnesium concentrations in newborns, children, and young adults and (2) evaluate the frequency and clinical implications of ionized hypomagnesemia in patients undergoing surgery for congenital heart disease. METHOD: We prospectively measured ionized magnesium concentrations in 299 subjects (113 control subjects and 186 patients undergoing surgery for congenital heart disease). Subjects were categorized by age. In the surgical group blood samples were obtained before bypass, during bypass (cooling and rewarming), after bypass, and during admission to the intensive care unit. Ionized hypomagnesemia was defined as ionized magnesium level 2 standard deviations below the mean of control subjects in the same age group. Patients were analyzed, controlling for cardiopulmonary bypass time. RESULTS: In the control group ionized magnesium concentrations differed by age. Neonates and adults showed lower ionized magnesium concentrations compared with those of other age groups. Infants exhibited the highest ionized magnesium concentration. In the surgical group patients older than 1 month showed a higher proportion of ionized hypomagnesemia compared with that found in neonates at baseline (P <.001), after bypass (P =. 03), and at admission to the intensive care unit (P =.02). Controlling for cardiopulmonary bypass time, patients older than 1 month who were hypomagnesemic during bypass showed longer intubation time (P =.001) and longer intensive care stay (P =.01) and tended to have a higher pediatric severity of illness score on intensive care admission (P =.14) compared with patients without ionized hypomagnesemia. CONCLUSIONS: There are age-related differences in normal ionized magnesium concentrations. Ionized hypomagnesemia is a common and clinically relevant occurrence among patients older than 1 month of age undergoing surgery for congenital heart disease.     

Perioperative coronary artery spasm in off-pump coronary artery bypass grafting and its possible relation with perioperative hypomagnesemia.

PURPOSE: We experienced 3 cases of serious perioperative coronary artery spasm in off-pump coronary artery bypass grafting (OPCAB). In consideration of the causes, we directed our attention to hypomagnesemia, one of the triggers of coronary artery spasm. This study was performed to confirm the tendency to hypomagnesemia in OPCAB. METHODS: First, we report 3 patients having severe coronary artery spasm immediately after OPCAB with consideration of the causes. Second, serial magnesium (Mg) value (xylidyl blue method, normal 1.9-3.1 mg/dl) was measured in 45 consecutive patients with OPCAB between April and October 2002, 1) before starting the operation, and 2) after the patient's entrance into the intensive care unit. RESULTS: Preoperative and postoperative values of Mg (mg/dl) were 2.1+/-0.3, 1.7+/-0.3, respectively (p < 0.01). Postoperative incidence of hypomagnesemia was as high as 89% of the patients (40 out of 45 patients). In this study and thereafter, we corrected hypomagnesemia with magnesium sulfate during and after OPCAB, and no perioperative coronary artery spasm occurred. CONCLUSION: Hypomagnesemia, one of the triggers of coronary artery spasm, is very common in OPCAB. We strongly recommend the correction of hypomagnesemia during and after OPCAB for the prevention of perioperative coronary artery spasm.     

Correction of thiazide-induced hypomagnesemia by potassium-magnesium citrate from review of prior trials

PURPOSE: To ascertain whether hypomagnesemia develops during short-term thiazide treatment in normal subjects and if it can be corrected by potassium-magnesium citrate (Relyte) supplementation. METHODS: Serum magnesium data were retrieved from 242 normal subjects from prior 4 trials. After 1-3 weeks of treatment with hydrochlorothiazide 50 mg/day, subjects received supplementation with Relyte or a related compound while continuing on thiazide for 3 weeks. RESULTS: Hypomagnesemia (< or =1.8 mg/dl) was disclosed in 19.4% of 242 subjects on thiazide alone. In such patients, Relyte treatment significantly increased serum magnesium concentration to the normal range, whereas supplementation with potassium citrate or potassium chloride did not. In the Relyte group comprised of 131 subjects, the frequency of hypomagnesemia decreased from 22.9% on thiazide alone to 4.6% after 4 weeks of Relyte supplementation. In contrast, the frequency of hypomagnesemia displayed a non-significant increase from 15.7% on thiazide alone to 20-24% on potassium citrate or potassium chloride. CONCLUSION: Mild hypomagnesemia develops in about one fifth of normal subjects during short-term thiazide treatment. Relyte can readily correct it.     

Admission hypomagnesemia--impact on mortality or morbidity in critically ill patients

BACKGROUND/OBJECTIVE: No previous study exists to evaluate admission serum magnesium level as a predictor of morbidity or mortality. The aim of this study was to define the prevalence of admission hypomagnesemia in critically ill patients and to evaluate its relationship with organ dysfunction, length of stay, and mortality. METHODS: A retrospective study was done on 100 patients > or =16 years old, admitted to the medical-surgical intensive care unit (ICU) at the University Hospital over 2 years period. Observations were made on admission total serum magnesium level, a variety of lab tests related to magnesium, need for ventilator, duration of mechanical ventilation, hospital/ICU lengths of stay, and general patient demographics. RESULTS: The serum magnesium level (normal value, 1.3-2.1 mEq/L) was measured at admission. At admission, 51% of patients had hypomagnesemia, 49% had normal magnesium levels. There was significant difference in mortality rate (55% vs 35%), the length of hospital (15.29 +/- 0.66 vs 12.81 +/- 0.91), or ICU (9.16 +/- 0.53 vs 5.71 +/- 0.55) stay between these two groups of patients (p < 0.05 for all). Hypomagnesemic patients more frequently had total hypocalcemia, hypokalemia, and hyponatremia. A total of 51 patients developed hypomagnesemia during their ICU stay; these patients had higher Acute Physiology And Chronic Health Evaluation II (APACHE II) (14.16 +/- 1.03 vs 10.80 +/- 0.94) and Sequential Organ Failure Assessment (SOFA; 10.89 +/- 0.90 vs 7.58 +/- 5.01) scores at admission (p < 0.01 for both), a higher maximum SOFA score during their ICU stay (14.75 +/- 0.73 vs 8.08 +/- 0.52, p < 0.01), a more need to ventilator (58.6% vs 41.4%, p < 0.05), and longer duration of mechanical ventilation (7.2 vs 4.7 day, p < 0.01) than the other patients. The ROC curve of SOFA score in the hypomagnesemia yields significantly better results than APACHE II. An increase of 5 units in the APACHE II or SOFA measured on admission increase relative probability of hypomagnesemia by a factor of 0.12 and 0.16 respectively. CONCLUSION: Development of hypomagnesemia during an ICU stay is associated with guarded prognosis. Monitoring of serum magnesium levels may have prognostic, and perhaps therapeutic, implications.     

Tacrolimus-associated hypomagnesemia in renal transplant recipients

BACKGROUND: Since hypomagnesemia occurs frequently in tacrolimus treated patients, we studied the correlation between renal magnesium wasting and tacrolimus blood levels in renal transplant patients. METHODS: Serum magnesium, fractional excretion of magnesium (FEMg), and 24-hour urinary excretion of magnesium were measured in 41 transplant patients and 10 healthy volunteers for correlation with tacrolimus level. RESULTS: Of tacrolimus-treated patients, 43% displayed hypomagnesemia. FEMg (7.42+/-3.59% versus 1.88+/-0.43%) and 24-hour urinary excretion (112.36+/-51.43 mg/dL versus 6.7+/-2.79 mg/dL) were significantly higher among tacrolimus-treated patients than controls. Magnesium replacement did not influence FEMg or 24-hour urinary magnesium excretion. Tacrolimus level was the best predictor of 24-hour urinary magnesium excretion and FEMg. Serum magnesium levels correlated inversely with tacrolimus concentrations and creatinine clearance. CONCLUSION: Hypomagnesemia in renal transplant recipients results from renal magnesium wasting. Tacrolimus levels and renal function impact on the excess renal magnesium excretion. Studies of longer duration are warranted to assess the long-term effects of this early posttransplant hypomagnesemia.     

Posttransplantation Hypomagnesemia and Its Relation with Immunosuppression as Predictors of New-Onset Diabetes after Transplantation

New-onset diabetes after transplantation (NODAT) is a frequent complication and has an impact on patient and graft survival. Hypomagnesemia is common in both renal transplant recipients and in diabetics. This study examines the relationship between hypomagnesemia, NODAT and the type of immunosuppression in renal transplant recipients.
We conducted a retrospective single-center analysis (2002–2008) in order to assess NODAT the first year posttransplantation as defined by American Diabetes Association criteria. Serum magnesium (Mg) levels were defined as the median of all Mg levels registered during the first month posttransplantation.
Patients with NODAT (N = 75; 29.5%) versus non-NODAT had lower Mg levels (p < 0.001). Patients with an Mg level < versus ≥1.9 mg/dL showed a faster development of NODAT (log-rank p < 0.001). Mg levels were lower in patients on calcineurin inhibitors (CNI) versus no CNI patients (p < 0.001). Mg levels, albumin, BMI, triglycerides, posttransplantation hyperglycemia, tacrolimus levels and the use of sirolimus were predictors of NODAT in the multivariate analysis.
Hypomagnesemia was an independent predictor of NODAT in renal transplant recipients. We confirm that the use of CNI is associated with NODAT, but, to a large extent, this effect seems attributable to the induction of hypomagnesemia. After adjustment for Mg, sirolimus was also associated with NODAT.     

Allogeneic activation is attenuated in a model of mouse lung perfused with magnesium-deficient blood

Hypomagnesemia, which is frequently observed in patients treated with calcineurin inhibitors to prevent rejection after allogeneic transplantation, has been associated with a faster rate of decline in allograft function. The effect of hypomagnesemia on lung allograft has not been reported yet. In our model of isolated mouse lung, we have evaluated the early effects of allogeneic lung perfusion with blood from magnesium (Mg)-deficient mice for 3 h on lung activation and remodelling, compared to isogeneic perfusion. Hypomagnesemia (0.21 ± 0.07 mmol Mg²⁺/l) was observed in blood from Mg-deficient mice, but no inflammatory pattern. The mRNA level of the intercellular adhesion molecule (ICAM)-1, but neither of the vascular cell adhesion molecule (VCAM)-1, nor of the cytokines tumor necrosis factor (TNF)α and interleukin (IL)-2, was enhanced (p < 0.05). Although caspase-3 mRNA was transiently enhanced, no apoptotic cells were evidenced in lung tissues even after 3 h. Using cDNA array, we found that the genes encoding RANKL, RANK, TNFR2, NFATX, IL-1R2, IL-6R gp130, SOCS3, PDGFRB, P63, CSF3R, CXCL1, CXCL5, CX3CL1, CSF1, which are involved in inflammation and apoptosis regulation, were markedly up-regulated in allogeneic conditions. Our results support a limited allogeneic activation and an early stage of the inflammatory process in lung, at the time of inflammatory cell recruitment without lung tissue remodelling, as a result of hypomagnesemia. These findings suggest that cyclosporine-related hypomagnesemia, observed in most of the transplanted patients, does not constitute an additional risk for lung allograft outcome.     

Hypomagnesemia and Hypocalcemia after Thyroidectomy: Prospective Study

Hypomagnesemia after total thyroidectomy has not been studied extensively. Our anecdotal experience suggests that it may be important in some patients after thyroid excision. The hypomagnesemic hypocalcemic syndrome has been described in other disease states in which a state of functional hypoparathyroidism exists. This study was designed to determine the incidence of hypomagnesemia after total thyroidectomy and relate it to hypocalcemia and symptoms during the postoperative period. A prospective study of all patients undergoing total thyroidectomy between September 1994 and July 1996 was performed. Patient data, thyroid function, retrosternal extension, initial versus reoperative surgery, operative details, parathyroid resection, and pathology were recorded. Calcium, magnesium, electrolytes, blood count, liver function tests, and albumin were measured prior to surgery and twice daily during the postoperative period. Fifty patients underwent total thyroidectomy: 68% were hypocalcemic, 72% were hypomagnesemic, and 36% were symptomatic during the postoperative period. Hypomagnesemia and gender were associated with hypocalcemia. Volume of fluid and neck dissection were associated with low magnesium levels. Hypomagnesemia and parathyroid resection were risk factors for symptoms after thyroidectomy. No patients developed permanent hypoparathyroidism. Transient hypocalcemia and hypomagnesemia occur frequently after total thyroidectomy. The etiology of this phenomenon is probably multifactorial. Patients are more likely to be symptomatic when both cations are low, and attempting to correct only hypocalcemia may prolong symptoms. It is important to monitor both calcium and magnesium levels after total thyroidectomy and to correct deficiencies to facilitate prompt resolution of symptoms.     

Pulmonary complications of aneurysmal subarachnoid hemorrhage

OBJECTIVE: Pulmonary complications challenge the medical management of patients who have sustained aneurysmal subarachnoid hemorrhage (SAH). We assessed the frequency and types of pulmonary complications after aneurysmal SAH and analyzed the impact of pulmonary complications on patient outcome. METHODS: We reviewed the records of all patients with acute SAH treated at our institution between 1990 and 1997. Three hundred five consecutive patients with an aneurysmal hemorrhage source documented by angiography and treated within 7 days of ictus were analyzed. Outcomes at longest follow-up (mean, 16 mo) were measured by use of the Glasgow Outcome Scale. RESULTS: Pulmonary complications were documented in 66 patients (22%). The pulmonary complications were nosocomial pneumonia in 26 patients (9%), congestive heart failure in 23 (8%), aspiration pneumonia in 17 (6%), neurogenic pulmonary edema in 5 (2%), pulmonary embolus in 2 (<1%), and other pulmonary disorders in 4 (1%); 11 patients had two pulmonary complications. The incidence of symptomatic vasospasm was greater in patients with pulmonary complications (63%) than in patients without pulmonary complications (31%) (P = 0.001), and this association was independent of age and clinical grade at admission (odds ratio, 3.68; P < 0.001). Overall clinical outcomes were worse in patients with pulmonary complications (mean Glasgow Outcome Scale score, 3.3) than in patients without pulmonary complications (mean Glasgow Outcome Scale score, 4.0; P = 0.0001), but pulmonary complications were not an independent predictor of worse outcome when adjusted for age and clinical grade at admission (odds ratio, 1.38; P = 0.315). CONCLUSION: Patients who experience pulmonary complications after aneurysmal SAH have a higher incidence of symptomatic vasospasm than do patients without pulmonary complications. This most likely reflects both the failure to maintain aggressive hypervolemic and hyperdynamic therapy in patients with pulmonary compromise and the possible precipitation of congestive heart failure by hypervolemic therapy in patients with preexisting delayed ischemic neurological deficit. Although patients with pulmonary complications have worse overall clinical outcomes than do patients without pulmonary complications, this is attributable to older age and worse clinical grades at admission.     

Long-term effects of nimodipine on cerebral infarcts and outcome after aneurysmal subarachnoid hemorrhage and surgery

A total of 213 patients with verified aneurysmal subarachnoid hemorrhage (SAH) of Grades I to III (Hunt and Hess classification) were enrolled in a double-blind placebo-controlled trial to determine the effect of intravenous nimodipine on delayed ischemic deterioration and computerized tomography (CT)-visualized infarcts after SAH and surgery. The administration of the drug or matching placebo was started immediately after the radiological diagnosis of a ruptured aneurysm had been made. Of the 213 patients enrolled in the study, 58 were operated on early (within 72 hours after the bleed: Days 0 to 3), 69 were operated on subacutely (between Days 4 and 7), and 74 had late surgery (on Day 8 or later). Eleven patients died before surgery was undertaken and one was not operated on. A follow-up examination with CT scanning, performed 1 to 3 years after the SAH (mean 1.4 years), revealed no significant differences in the overall outcome between the groups. However, nimodipine treatment was associated with a significantly lower incidence of deaths caused by delayed cerebral ischemia (p = 0.01) and significantly lower occurrence of cerebral infarcts visualized by CT scanning in the whole population (p = 0.05), especially in patients without an associated intracerebral hemorrhage on admission CT scan (p = 0.03).     

Preclinical and clinical role of interleukin-6 in the development of delayed cerebral vasospasm and neuronal cell death after subarachnoid hemorrhage: towards a potential target therapy?

Delayed cerebral vasospasm (DCVS), early brain injury (EBI), and delayed cerebral ischemia (DCI) are devastating complications after aneurysmal subarachnoid hemorrhage (SAH). Interleukin (IL)-6 seems to be an important interleukin in the inflammatory response after SAH, and many studies describe a strong correlation between IL-6 and worse outcome. The aim of this study was to systematically review preclinical and clinical studies that evaluated systemic and cerebral IL-6 levels after SAH and their relation to DCVS, neuronal cell death, and DCI. We conducted two systematic literature searches using PubMed to identify preclinical and clinical studies evaluating the role of IL-6 after SAH. Suitable articles were selected based on predefined eligibility criteria following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 61 and 30 preclinical and clinical articles, respectively, were included in the systematic reviews. Of the preclinical studies in which IL-6 was measured in cerebrospinal fluid (CSF), parenchyma, and systemically, 100%, 94.4%, and 81.3%, respectively, showed increased expression of IL-6 after SAH. Preclinical results were mirrored by clinical findings in which elevated levels of IL-6 in CSF and plasma were found after SAH, correlating with DCVS, DCI, and worse outcome. Only two preclinical studies analyzed the direct inhibition of IL-6, which resulted in reduced DCVS and neuronal cell death. IL-6 is a marker of intracranial inflammation and plays a role in the pathophysiology of DCVS and DCI after SAH in preclinical animal models and clinical studies. Its inhibition might have therapeutic potential to improve the outcome of SAH patients.

     

In vitro analysis of platelet function in acute aneurysmal subarachnoid haemorrhage

Platelet function might play an essential role in the pathogenesis of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (SAH). Thus, impaired platelet function and disturbed primary haemostasis induced by intake of acetylsalicylic acid (ASA) might influence the rate of DCI. Primary haemostasis and platelet function can be measured with in vitro diagnosis (platelet function analyser test, PFA 100). The aim of this study is to evaluate the rate of DCI, haemorrhagic complications and the neurological outcome. Two groups were compared (patients with regular platelet function versus patients with impaired platelet function). This is a retrospective observational study. An initial cohort of 787 patients with SAH has been treated from January 2005 to September 2012. Seventy-nine patients (10%) with aneurysmal SAH, a history of ASA medication and PFA testing within the first 24 h after aneurysm rupture have been included. The overall rate of DCI in the present study was 43%. In vitro platelet function testing showed pathological primary haemostasis in 69.6%. The DCI rate was higher in patients with regular tested primary haemostasis (p = 0.02, OR = 3.16, 95%CI = [1.19; 8.83]). However, outcome assessment by mGOS did not show a significant difference between the groups. Patients with impaired primary haemostasis did not display a higher rate of haemorrhagic complications. Impairment of primary haemostasis resulting from an impairment of platelet function at an early stage after SAH might lead to a lower rate of DCI. In vitro testing of platelet function might be useful to predict the occurrence of DCI in the course.     

Predicting the overall management outcome in patients with a subarachnoid hemorrhage accompanied by a massive intracerebral or full-packed intraventricular hemorrhage: a 15-year retrospective study

BACKGROUND: Patients with a subarachnoid hemorrhage (SAH) accompanied by a massive intracerebral hemorrhage (ICH) or a full-packed intraventricular hemorrhage (IVH) have poor outcomes. We evaluated the clinical factors to predict the overall outcome in such patients. METHODS: Data on nontraumatic SAH patients were collected and classified into 3 groups: the pure SAH group (SAH accompanied with neither ICH nor IVH), the ICH group (SAH accompanied with a massive ICH; hematoma 30 mL), and the IVH group (SAH and all ventricles were full-packed with hematoma). One hundred seventy-nine patients were in the ICH group and 109 in the IVH group. We evaluated clinical factors, such as the Hunt & Hess (H&H) score on admission, age, sex, history, rebleeding ratio, and the computerized tomography findings (SAH score). RESULTS: The result of multivariate logistic regression analysis of clinical variables in the ICH group, good and intermediate H&H grades, younger age (<70), no rebleeding, and lower SAH score were associated with a favorable outcome. In the result of the multivariate logistic regression analysis of clinical variables in the IVH group, only a higher SAH score was associated with an unfavorable outcome. CONCLUSIONS: In the ICH group, factors that could be used to predict a favorable outcome included good and intermediate H&H scores (1, 2, and 3) on admission, younger age (<70), and a lower SAH score. In the IVH group, the main factor that could be used to predict a favorable outcome was a lower SAH score.     

Long-term outcome of surgically treated patients with corrected transposition of the great arteries

OBJECTIVES: The purpose of the study was to examine long-term outcome after traditional surgical treatment of corrected transposition of the great arteries to provide a basis for comparison with new procedures, such as the double-switch or Senning-Rastelli procedures. METHODS: Patient- and procedure-related variables in 123 patients with corrected transposition and 2 functional ventricles operated on between 1963 and 1996 were analyzed. Patients with intracardiac procedures underwent either a traditional 2-ventricle repair or a Fontan procedure. RESULTS: The 1-, 5-, 10-, and 15-year survivals after the operation were 84%, 75%, 68%, and 61%, respectively. Patients requiring tricuspid valve replacement (27 patients) at any time during follow-up had a significantly worse outcome ( P < .001; hazard ratio, 4.4), whereas the best outcome was seen in patients undergoing the Fontan procedure (17 patients, 0 deaths). Right ventricular end-diastolic pressure of greater than 17 mm Hg before the operation ( P < .0001), complete heart block after the operation ( P = .001), subvalvular pulmonary stenosis ( P = .013), Ebstein malformation of the tricuspid valve ( P = .025), and preoperative systemic (right) ventricular dysfunction ( P = .041) were identified as risk factors for death at any time by means of univariate analysis. Ebstein malformation of the tricuspid valve ( P = .036; hazard ratio, 1.5) was identified as a risk factor for death by multivariate analysis. CONCLUSIONS: The long-term outcome of patients with corrected transposition after a classic surgical approach is unsatisfactory. The poorest outcome was seen in patients who required tricuspid valve replacement either at their initial operation or later during follow-up. Alternative surgical approaches, such as the double-switch, Senning-Rastelli, or Fontan procedures, are likely to have better long-term results, especially in the highest risk groups.