Safety of Abciximab injection during endovascular treatment of ruptured aneurysms

Background and purpose

We aimed to determine the safety of intra-arterial Abciximab injection in the management of thromboembolic complications during endovascular treatment of ruptured cerebral aneurysms.

Methods

In a monocentric consecutive series of endovascular treatment of 783 ruptured aneurysms, 42 (5.3%) patients received Abciximab after the aneurysm was secured. Bleeding complications were registered and dichotomized as follows: new intracranial hemorrhage and peripheral bleeding. For each patient, World Federation of Neurosurgery (WFNS) subarachnoid hemorrhage (SAH) grade, shunting, and clinical outcomes in the post-operative period and at 3–6 months were recorded.

Results

SAH WFNS grades were as follows: grade I n = 14, grade II n = 10, grade III n = 11, grade IV n = 4, grade V n = 3. Ten patients had intracranial hematoma additionally to the SAH prior to embolization. Four patients (9.5%) presented more blood on the post-embolization CT but only one suffered a new clinically relevant intracranial hemorrhage. Two patients (4.8%) experienced significant peripheral bleeding but none were associated with long-term disabilities. Fourteen patients had a shunt installed less than 24 h prior to Abciximab injection and one less than 48 h later. At 3–6-month follow-up, 31 patients (74%) achieved a modified Rankin Scale score (mRS) of 2 or less, six patients (14%) had a mRS of 3–5, three were dead (7%), and two were lost at follow-up.

Conclusion

When the aneurysm is secured, intra-arterial Abciximab injection is a low complication rate treatment modality for thromboembolic events during embolization of cerebral ruptured aneurysm.     

Risk factors for coil protrusion into the parent artery and associated thrombo-embolic events following unruptured cerebral aneurysm embolization

Objective

Advances in vascular reconstruction devices and coil technologies have made coil embolization a popular and effective strategy for treatment of relatively wide-neck cerebral aneurysms. However, coil protrusion occurs occasionally, and little is known about the frequency, the risk factors and the risk of thrombo-embolic complications.

Method

We assessed the frequency and the risk factors for coil protrusion in 330 unruptured aneurysm embolization cases, and examined the occurrence of cerebral infarction by diffusion-weighted magnetic resonance imaging (DW-MRI).

Result

Forty-four instances of coil protrusion were encountered during coil embolization (13.3% of cases), but incidence was reduced to 33 (10% of cases) by balloon press or insertion of the next coil. Coil protrusion occurred more frequently during the last phase of the procedure, and both a wide neck (large fundus to neck ratio) (OR = 1.84, P = 0.03) and an inadequately stable neck frame (OR = 5.49, P = 0.0007) increased protrusion risk. Coil protrusions did not increase the incidence of high-intensity lesions (infarcts) on DW-MRI (33.3% vs 29% of cases with no coil protrusion). However, longer operation time did increase infarct risk (P = 0.0003). Thus, tail or loop type coil protrusion did not increase the risk of thrombo-embolic complications, if adequate blood flow was maintained.

Conclusion

Coil protrusion tended to occur more frequently in cases of wide-neck aneurysms with loose neck framing. Moderate and less coil protrusion carries no additional thrombo-embolic risk, if blood flow is maintained, which can be aided by additional post-operative antiplatelet therapy.     

Use of a new soft and long coil reduces the number of coils to embolize a small aneurysm

Background

In embolizing a cerebral aneurysm, achievement of a high-volume embolization ratio (VER: volume of inserted coils / aneurysm volume) is important because it may prevent coil compaction and recanalization. The goal of the study is to examine whether use of softer and longer coils gives an adequate VER with fewer coils, particularly for small aneurysms.

Methods

Aneurysm volumes, VERs, and numbers of inserted coils were investigated in 23 cases of small aneurysms embolized using Infini coils, a long soft coil with a primary diameter of 0.010 inches (Infini group). An aneurysm volume- and VER-matched control (non-Infini) group of 59 cases was selected from patients treated at our facility. Data were also compared between subgroups of patients (n = 18 and n = 34 in the Infini and non-Infini groups, respectively) who were not treated with thicker coils with primary diameters of 0.0135–0.015 inches (18-type coils), since these coils affect the number of coils by increasing VER rapidly.

Results

Average aneurysm volumes and VERs did not differ significantly between the Infini and non-Infini groups. Significantly fewer coils were used per 0.1 ml aneurysm volume in the Infini group (4.08 coils in average) compared with the non-Infini group (5.67) (p < 0.001). In the non-18-type subgroups, the number of coils used remained significantly smaller in the Infini group (4.49) compared with the non-Infini group (6.72), (p < 0.001).

Conclusion

To achieve VER ≥20%, use of Infini coils significantly decreased the number of coils required per unit volume of a small aneurysm.     

Emergent extracranial internal carotid artery stenting and mechanical thrombectomy in acute ischaemic stroke

Objective

Tandem occlusions involving both the extracranial internal carotid artery (ICA) and an intracranial artery typically respond poorly to intravenous (IV) tissue plasminogen activator (t-PA). We retrospectively review our experience with proximal ICA stenting and stent-assisted thrombectomy of the distal artery.

Methods

The data included patients that underwent carotid stenting and mechanical thrombectomy between 2012–2013. Radiographic, clinical, and procedural data were drawn from case notes, imaging records and discharge reports. Clinical outcomes were evaluated using the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin scale (mRs).

Results

Seven patients, with a mean age of 66.4 years and a mean admission NIHSS of 18.3, underwent this procedure and were included. Each presented with an occlusion of the proximal ICA, with additional occlusions of the ICA terminus (n = 3), middle cerebral artery (n = 5), or anterior cerebral artery (n = 1). Recanalisation of all identified occlusions was achieved in all patients, with a Thrombolysis in Myocardial Infarction (TIMI) score of 3 and a Thrombolysis in Cerebral Infarction (TICI) score >2b achieved in each case. Mean time from onset of stroke symptoms to recanalisation was 287 min; mean time from first angiography to recanalisation was 52 min. Intracranial haemorrhages occurred in two patients, with no increase in NIHSS. There were no mortalities. Mean NIHSS at discharge was 4.9, and mRs at 90 days was one in all patients.

Conclusions

Treatment of tandem extracranial ICA and intracranial occlusions in the setting of acute ischaemic stroke with extracranial carotid artery stenting followed by adjunctive intracranial mechanical thrombectomy is both safe and effective, but further evaluation of this treatment modality is necessary.     

The safety and efficacy of preoperative embolization of meningioma with N-butyl cyanoacrylate

Objective

Preoperative embolization of meningioma is commonly performed; however, there is no consensus on the best embolic material to reduce intraoperative blood loss and surgery time.

Method

We retrospectively assessed the safety and efficacy of 56 cases of preoperative embolization of the middle meningeal artery with N-butyl cyanoacrylate (NBCA) in 105 cases of surgery for meningioma. We also defined a blood loss to tumor volume ratio to compensate for bias caused by tumor volume, and analyzed limited cases (the embolized group n = 52, the non-embolized group n = 21) of the convexity, the parasagittal region, the falx, and the sphenoidal ridge.

Result

The blood loss to tumor volume ratio was significantly less in the embolized group (p < 0.007). Preoperative embolization could be useful for cases with the external carotid artery as the dominant feeder vessel (p < 0.02); however, the efficacy decreased for cases with an internal carotid artery feeder. Transient complications occurred in four cases (hemiparesis secondary to edema: two cases; intratumoral bleeding: one case; trigeminal nerve disorder: one case). The cases that showed a postoperative increase in edema or intratumoral bleeding were large tumors with the early filling of veins. For such cases, surgeons should pay close attention to slow injection speed and higher NBCA viscosity, not to cause the occlusion of draining vessels.

Conclusion

Tumor embolization with NBCA can be safely performed, and the procedure significantly reduces intraoperative blood loss.     

Clinical and angiographic outcomes of stent-assisted coiling of intracranial aneurysms

Background

Despite the increasing use of stent-assisted coiling (SAC), data on its long-term clinical and angiographic results are limited.

Objective

The objective of this article is to assess the long-term clinical and angiographic outcomes in SAC in our single-center practice.

Methods

We conducted a retrospective analysis of intracranial aneurysms treated with detachable coils during the period 2003–2012. Patients were divided into SAC and non-SAC groups and were analyzed for aneurysm occlusion, major recurrence and clinical outcome. Logistic regression analyses identified factors associated with clinical/angiographic outcomes (p value <0.05 was statistically significant).

Results

A total of 516 procedures met inclusion criteria: Sixty-three (12.2%) patients underwent SAC, of whom 56 (89%) had an elective procedure whereas 286 (63.1%) aneurysms from the non-SAC group were ruptured. In the unruptured subcohort, baseline class I was achieved in 24 (38%, p = 0.91), and predischarge modified Rankin scale score (mRS) 0–2 was obtained in 96.4% of cases in the SAC group versus 90.4% in the non-stent group. The major recurrence was 9.5% versus 11.3% in the SAC and non-SAC group, respectively (p = 0.003). At last clinical assessment, 98.2% of the patients from the unruptured SAC group had mRS 0–2 (mean follow-up, 58 months) versus 93.6% (mean follow-up, 56 months) in the unruptured non-SAC group (p = 0.64). Periprocedural vasospasm was associated with long-term poor outcome in the unruptured SAC subcohort (p = 0.0008).

Conclusions

SAC and non-SCA techniques show comparable safety and clinical outcome. The SAC technique significantly decreases retreatment rates. Periprocedural vasospasm resulting from vessel manipulation is associated with poor outcome in SAC of unruptured aneurysms.     

Extracorporeal membrane oxygenation in adult patients with hematologic malignancies and severe acute respiratory failure

Introduction

Acute respiratory failure (ARF) is the main reason for intensive care unit (ICU) admissions in patients with hematologic malignancies (HMs). We report the first series of adult patients with ARF and HMs treated with extracorporeal membrane oxygenation (ECMO).

Methods

This is a retrospective cohort study of 14 patients with HMs (aggressive non-Hodgkin lymphoma (NHL) n = 5; highly aggressive NHL, that is acute lymphoblastic leukemia or Burkitt lymphoma, n = 5; Hodgkin lymphoma, n = 2; acute myeloid leukemia, n = 1; multiple myeloma, n = 1) receiving ECMO support because of ARF (all data as medians and interquartile ranges; age, 32 years (22 to 51 years); simplified acute physiology score II (SAPS II): 51 (42 to 65)). Etiology of ARF was pneumonia (n = 10), thoracic manifestation of NHL (n = 2), sepsis of nonpulmonary origin (n = 1), and transfusion-related acute lung injury (n = 1). Diagnosis of HM was established during ECMO in four patients, and five first received (immuno-) chemotherapy on ECMO.

Results

Before ECMO, the PaO₂/FiO₂ ratio was 60 (53 to 65), (3.3 to 3.7). Three patients received venoarterial ECMO because of acute circulatory failure in addition to ARF; all other patients received venovenous ECMO. All patients needed vasopressors, and five needed hemofiltration. Thrombocytopenia occurred in all patients (lowest platelet count was 20 (11 to 21) G/L). Five major bleeding events were noted. ECMO duration was 8.5 (4 to 16) days. ICU and hospital survival was 50%. All survivors were alive at follow-up (36 (10 to 58) months); five patients were in complete remission, one in partial remission, and one had relapsed.

Conclusions

ECMO therapy is feasible in selected patients with HMs and ARF and can be associated with long-term disease-free survival.     

The effect of prone positioning on mortality in patients with acute respiratory distress syndrome: a meta-analysis of randomized controlled trials

Introduction

Prone positioning (PP) has been reported to improve the survival of patients with severe acute respiratory distress syndrome (ARDS). However, it is uncertain whether the beneficial effects of PP are associated with positive end-expiratory pressure (PEEP) levels and long durations of PP. In this meta-analysis, we aimed to evaluate whether the effects of PP on mortality could be affected by PEEP level and PP duration and to identify which patients might benefit the most from PP.

Methods

Publications describing randomized controlled trials (RCTs) in which investigators have compared prone and supine ventilation were retrieved by searching the following electronic databases: PubMed/MEDLINE, the Cochrane Library, the Web of Science and Elsevier Science (inception to May 2013). Two investigators independently selected RCTs and assessed their quality. The data extracted from the RCTs were combined in a cumulative meta-analysis and analyzed using methods recommended by the Cochrane Collaboration.

Results

A total of nine RCTs with an aggregate of 2,242 patients were included. All of the studies received scores of up to three points using the methods recommended by Jadad et al. One trial did not conceal allocation. This meta-analysis revealed that, compared with supine positioning, PP decreased the 28- to 30-day mortality of ARDS patients with a ratio of partial pressure of arterial oxygen/fraction of inspired oxygen ≤100 mmHg (n = 508, risk ratio (RR) = 0.71, 95 confidence interval (CI) = 0.57 to 0.89; P = 0.003). PP was shown to reduce both 60-day mortality (n = 518, RR = 0.82, 95% CI = 0.68 to 0.99; P = 0.04) and 90-day mortality (n = 516, RR = 0.57, 95% CI = 0.43 to 0.75; P < 0.0001) in ARDS patients ventilated with PEEP ≥10 cmH₂O. Moreover, PP reduced 28- to 30-day mortality when the PP duration was >12 h/day (n = 1,067, RR = 0.73, 95% CI = 0.54 to 0.99; P = 0.04).

Conclusions

PP reduced mortality among patients with severe ARDS and patients receiving relatively high PEEP levels. Moreover, long-term PP improved the survival of ARDS patients.     

Health-related quality of life scores after intensive care are almost equal to those of the normal population: a multicenter observational study

Introduction

Health-related quality of life (HRQoL) in patients treated in intensive care has been reported to be lower compared with age- and sex-adjusted control groups. Our aim was to test whether stratifying for coexisting conditions would reduce observed differences in HRQoL between patients treated in the ICU and a control group from the normal population. We also wanted to characterize the ICU patients with the lowest HRQoL within these strata.

Methods

We did a cross-sectional comparison of scores of the short-form health survey (SF-36) questionnaire in a multicenter study of patients treated in the ICU (n = 780) and those from a local public health survey (n = 6,093). Analyses were in both groups adjusted for age and sex, and data stratified for coexisting conditions. Within each stratum, patients with low scores (below -2 SD of the control group) were identified and characterized.

Results

After adjustment, there were minor and insignificant differences in mean SF-36 scores between patients and controls. Eight (n = 18) and 22% (n = 51) of the patients had low scores (-2 SD of the control group) in the physical and mental dimensions of SF-36, respectively. Patients with low scores were usually male, single, on sick leave before admission to critical care, and survived a shorter time after being in ICU.

Conclusions

After adjusting for age, sex, and coexisting conditions, mean HRQoL scores were almost equal in patients and controls. Up to 22% (n = 51) of the patients had, however, a poor quality of life as compared with the controls (-2 SD). This group, which more often consisted of single men, individuals who were on sick leave before admission to the ICU, had an increased mortality after ICU. This group should be a target for future support.     

Histological Validation of measurement of diffuse interstitial myocardial fibrosis by myocardial extravascular volume fraction from Modified Look-Locker imaging (MOLLI) T1 mapping at 3?T

Background

Gadolinium (Gd) Extracellular volume fraction (ECV) by Cardiovascular Magnetic Resonance (CMR) has been proposed as a non-invasive method for assessment of diffuse myocardial fibrosis. Yet only few studies used 3 T CMR to measure ECV, and the accuracy of ECV measurements at 3 T has not been established. Therefore the aims of the present study were to validate measurement of ECV by MOLLI T1 mapping by 3 T CMR against fibrosis measured by histopathology. We also evaluated the recently proposed hypothesis that native-T1 mapping without contrast injection would be sufficient to detect fibrosis.

Methods

31 patients (age = 58 ± 17 years, 77 % men) with either severe aortic stenosis (n = 12) severe aortic regurgitation (n = 9) or severe mitral regurgitation (n = 10), all free of coronary artery disease, underwent 3 T-CMR with late gadolinium enhancement (LGE) and pre- and post-contrast MOLLI T1 mapping and ECV computation, prior to valve surgery. LV biopsies were performed at the time of surgery, a median 13 [1–30] days later, and stained with picrosirius red. Pre-, and post-contrast T1 values, ECV, and amount of LGE were compared against magnitude of fibrosis by histopathology by Pearson correlation coefficients.

Results

The average amount of interstitial fibrosis by picrosirius red staining in biopsy samples was 6.1 ± 4.3 %. ECV computed from pre-post contrast MOLLI T1 time changes was 28.9 ± 5.5 %, and correlated (r = 0.78, p < 0.001) strongly with the magnitude of histological fibrosis. By opposition, neither amount of LGE (r = 0.17, p = 0.36) nor native pre-contrast myocardial T1 time (r = −0.18, p = 0.32) correlated with fibrosis by histopathology.

Conclusions

ECV determined by 3 T CMR T1 MOLLI images closely correlates with histologically determined diffuse interstitial fibrosis, providing a non-invasive estimation for quantification of interstitial fibrosis in patients with valve diseases. By opposition, neither non-contrast T1 times nor the amount of LGE were indicative of the magnitude of diffuse interstitial fibrosis measured by histopathology.     

Lipopolysaccharide infusion enhances dynamic cerebral autoregulation without affecting cerebral oxygen vasoreactivity in healthy volunteers

Introduction

Sepsis may be associated with disturbances in cerebral oxygen transport and cerebral haemodynamic function, thus rendering the brain particularly susceptible to hypoxia. The purpose of this study was to assess the impact of isocapnic hypoxia and hyperoxia on dynamic cerebral autoregulation in a human-experimental model of the systemic inflammatory response during the early stages of sepsis.

Methods

A total of ten healthy volunteers were exposed to acute isocapnic inspiratory hyperoxia (F_IO₂ = 40%) and hypoxia (F_IO₂ = 12%) before and after a 4-hour lipopolysaccharide (LPS) infusion (2 ng kg^-1). Middle cerebral artery blood follow velocity was assessed using transcranial Doppler ultrasound, and dynamic autoregulation was evaluated by transfer function analysis.

Results

Transfer function analysis revealed an increase in the phase difference between mean arterial blood pressure and middle cerebral artery blood flow velocity in the low frequency range (0.07–0.20 Hz) after LPS (P<0.01). In contrast, there were no effects of either isocapnic hyperoxia or hypoxia on dynamic autoregulation, and the cerebral oxygen vasoreactivity to both hyperoxia and hypoxia was unaffected by LPS.

Conclusions

The observed increase in phase suggests that dynamic cerebral autoregulation is enhanced after LPS infusion and resistant to any effects of acute hypoxia; this may protect the brain from ischaemia and/or blood–brain barrier damage during the early stages of sepsis.     

Optimal cerebral perfusion pressure in patients with intracerebral hemorrhage: an observational case series

Introduction

Current guidelines for spontaneous intracerebral hemorrhage (ICH) recommend maintaining cerebral perfusion pressure (CPP) between 50 and 70 mmHg, depending on the state of autoregulation. We continuously assessed dynamic cerebral autoregulation and the possibility of determination of an optimal CPP (CPPopt) in ICH patients. Associations between autoregulation, CPPopt and functional outcome were explored.

Methods

Intracranial pressure (ICP), mean arterial pressure (MAP) and CPP were continuously recorded in 55 patients, with 38 patients included in the analysis. The pressure reactivity index (PRx) was calculated as moving correlation between MAP and ICP. CPPopt was defined as the CPP associated with the lowest PRx values. CPPopt was calculated using hourly updated of 4 hour windows. The modified Rankin Scale (mRS) was assessed at 3 months and associations between PRx, CPPopt and outcomes were explored using Pearson correlation and Fisher’s exact test. Multivariate stepwise logistic regression models were calculated including standard outcome predictors along with percentage of time with PRx >0.2 and percentage of time within the CPPopt range.

Results

An overall PRx indicating impairment of pressure reactivity was found in 47% of patients (n = 18). The mean PRx and the time spent with a PRx > 0.2 significantly correlated with mRS at 3 months (r = 0.50, P = 0.002; r = 0.46, P = 0.004). CPPopt was calculable during 57% of the monitoring time. The median CPP was 78 mmHg, the median CPPopt 83 mmHg. Mortality was lowest in the group of patients with a CPP close to their CPPopt. However, for none of the CPPopt variables a significant association to outcome was found. The percentage of time with impaired autoregulation and hemorrhage volume were independent predictors for acceptable outcome (mRS 1 to 4) at three months.

Conclusions

Failure of pressure reactivity seems common following severe ICH and is associated with unfavorable outcome. Real-time assessment of CPPopt is feasible in ICH and might provide a tool for an autoregulation-oriented CPP management. A larger trial is needed to explore if a CPPopt management results in better functional outcomes.     

The plasma level and biomarker value of neutrophil gelatinase-associated lipocalin in critically ill patients with acute kidney injury are not affected by continuous venovenous hemofiltration and anticoagulation applied

Introduction

Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury (AKI), and levels reflect severity of disease in critically ill patients. However, continuous venovenous hemofiltration (CVVH) may affect plasma levels by clearance or release of NGAL by activated neutrophils in the filter, dependent on the anticoagulation regimen applied. We therefore studied handling of NGAL by CVVH in patients with AKI.

Methods

Immediately before initiation of CVVH, prefilter blood was drawn. After 10, 60, 180, and 720 minutes of CVVH, samples were collected from pre- and postfilter (in- and outlet) blood and ultrafiltrate. CVVH with the following anticoagulation regimens was studied: no anticoagulation in case of a high bleeding tendency (n = 13), unfractionated heparin (n = 8), or trisodium citrate (n = 21). NGAL levels were determined with enzyme-linked immunosorbent assay (ELISA).

Results

Concentrations of NGAL at inlet and outlet were similar, and concentrations did not change over time in any of the anticoagulation groups; thus no net removal or production of NGAL occurred. Concentrations of NGAL at inlet correlated with disease severity at initiation of CVVH and at the end of a CVVH run. Concentrations of NGAL in the ultrafiltrate were lower with citrate-based CVVH (P = 0.03) and decreased over time, irrespective of anticoagulation administered (P < 0.001). The sieving coefficient and clearance of NGAL were low and decreased over time (P < 0.001).

Conclusions

The plasma level and biomarker value of NGAL in critically ill patients with AKI are not affected by CVVH, because clearance by the filter was low. Furthermore, no evidence exists for intrafilter release of NGAL by neutrophils, irrespective of the anticoagulation method applied.     

Effect of admission time on mortality in an intensive care unit in Mainland China: a propensity score matching analysis

Introduction

The relationship between admission time and intensive care unit (ICU) mortality is inconclusive and influenced by various factors. This study aims to estimate the effect of admission time on ICU outcomes in a tertiary teaching hospital in China by propensity score matching (PSM) and stratified analysis.

Methods

A total of 2,891 consecutive patients were enrolled in this study from 1 January 2009 to 29 December 2011. Multivariate logistic regression and survival analysis were performed in this retrospective study. PSM and stratified analysis were applied for confounding factors, such as Acute Physiology and Chronic Health Evaluation II (APACHE II) score and admission types.

Results

Compared with office hour subgroup (n = 2,716), nighttime (NT, n = 175) subgroup had higher APACHE II scores (14 vs. 8, P < 0.001), prolonged length of stay in the ICU (42 vs. 24 h, P = 0.011), and higher percentages of medical (8.6% vs. 3.3%, P < 0.001) and emergency (59.4% vs. 12.2%, P < 0.001) patients. Moreover, NT admissions were related to higher ICU mortality [odds ratio (OR), 1.725 (95% CI 1.118–2.744), P = 0.01] and elevated mortality risk at 28 days [14.3% vs. 3.2%; OR, 1.920 (95% CI 1.171–3.150), P = 0.01]. PSM showed that admission time remained related to ICU outcome (P = 0.045) and mortality risk at 28 days [OR, 2.187 (95% CI 1.119–4.271), P = 0.022]. However, no mortality difference was found between weekend and workday admissions (P = 0.849), even if weekend admissions were more related to higher APACHE II scores compared with workday admissions.

Conclusions

NT admission was associated with poor ICU outcomes. This finding may be related to shortage of onsite intensivists and qualified residents during NT. The current staffing model and training system should be improved in the future.     

Optimal dosing of antibiotics in critically ill patients by using continuous/extended infusions: a systematic review and meta-analysis

Introduction

The aim of this study was to determine whether using pharmacodynamic-based dosing of antimicrobials, such as extended/continuous infusions, in critically ill patients is associated with improved outcomes as compared with traditional dosing methods.

Methods

We searched Medline, HealthStar, EMBASE, Cochrane Clinical Trial Registry, and CINAHL from inception to September 2013 without language restrictions for studies comparing the use of extended/continuous infusions with traditional dosing. Two authors independently selected studies, extracted data on methodology and outcomes, and performed quality assessment. Meta-analyses were performed by using random-effects models.

Results

Of 1,319 citations, 13 randomized controlled trials (RCTs) (n = 782 patients) and 13 cohort studies (n = 2,117 patients) met the inclusion criteria. Compared with traditional non-pharmacodynamic-based dosing, RCTs of continuous/extended infusions significantly reduced clinical failure rates (relative risk (RR) 0.68; 95% confidence interval (CI) 0.49 to 0.94, P = 0.02) and intensive care unit length of stay (mean difference, −1.5; 95% CI, −2.8 to −0.2 days, P = 0.02), but not mortality (RR, 0.87; 95% CI, 0.64 to 1.19; P = 0.38). No significant between-trial heterogeneity was found for these analyses (I² = 0). Reduced mortality rates almost achieved statistical significance when the results of all included studies (RCTs and cohort studies) were pooled (RR, 0.83; 95% CI, 0.69 to 1.00; P = 0.054).

Conclusions

Pooled results from small RCTs suggest reduced clinical failure rates and intensive care unit length-of-stay when using continuous/extended infusions of antibiotics in critically ill patients. Reduced mortality rates almost achieved statistical significance when the results of RCTs were combined with cohort studies. These results support the conduct of adequately powered RCTs to define better the utility of continuous/extended infusions in the era of antibiotic resistance.     

Free breathing contrast-enhanced time-resolved magnetic resonance angiography in pediatric and adult congenital heart disease

Background

Contrast enhanced magnetic resonance angiography (MRA) is generally performed during a long breath-hold (BH), limiting its utility in infants and small children. This study proposes a free-breathing (FB) time resolved MRA (TRA) technique for use in pediatric and adult congenital heart disease (CHD).

Methods

A TRA sequence was developed by combining spiral trajectories with sensitivity encoding (SENSE, x4 kx-ky and x2 kz) and partial Fourier (75% in kz). As no temporal data sharing is used, an independent 3D data set was acquired every ~1.3s, with acceptable spatial resolution (~2.3x2.3x2.3mm). The technique was tested during FB over 50 consecutive volumes. Conventional BH-MRA and FB-TRA data was acquired in 45 adults and children with CHD. We calculated quantitative image quality for both sequences. Diagnostic accuracy was assessed in all patients from both sequences. Additionally, vessel measurements were made at the sinotubular junction (N = 43), proximal descending aorta (N = 43), descending aorta at the level of the diaphragm (N = 43), main pulmonary artery (N = 35), left pulmonary artery (N = 35) and the right pulmonary artery (N = 35). Intra and inter observer variability was assessed in a subset of 10 patients.

Results

BH-MRA had significantly higher homogeneity in non-contrast enhancing tissue (coefficient of variance, P <0.0001), signal-to-noise ratio (P <0.0001), contrast-to-noise ratio (P <0.0001) and relative contrast (P = 0.02) compared to the FB-TRA images. However, homogeneity in the vessels was similar in both techniques (P = 0.52) and edge sharpness was significantly (P <0.0001) higher in FB-TRA compared to BH-MRA. BH-MRA provided overall diagnostic accuracy of 82%, and FB-TRA of 87%, with no statistical difference between the two sequences (P = 0.77). Vessel diameter measurements showed excellent agreement between the two techniques (r = 0.98, P <0.05), with no bias (0.0mm, P = 0.71), and clinically acceptable limits of agreement (-2.7 to +2.8mm). Inter and intra observer reproducibility showed good agreement of vessel diameters (r>0.988, P<0.0001), with negligible biases (between -0.2 and +0.1mm) and small limits of agreement (between -2.4 and +2.5mm).

Conclusions

We have described a FB-TRA technique that is shown to enable accurate diagnosis and vessel measures compared to conventional BH-MRA. This simplifies the MRA technique and will enable angiography to be performed in children and adults whom find breath-holding difficult.

Electronic supplementary material

The online version of this article (doi:10.1186/s12968-015-0138-9) contains supplementary material, which is available to authorized users.     

A common cause of sudden and thunderclap headaches: reversible cerebral vasoconstriction syndrome

Background

Thunderclap headache (TCH) is a sudden headache (SH) with accepted criteria of severe intensity and onset to peak within one minute. It is a well-known presentation for subarachnoid hemorrhage (SAH) but most patients with TCH or SH run a benign course without identifiable causes. Reversible cerebral vasoconstriction syndrome (RCVS), a recently recognized syndrome characterized by recurrent TCH attacks, has been proposed to account for most of these patients.

Methods

We recruited consecutive patients presenting with SH at our headache clinic. Computed tomography and/or magnetic resonance imaging with angiography were performed to exclude structural causes and to identify vasoconstriction. Catheter angiography and lumbar puncture were performed with patients consent. Reversibility of vasoconstriction was confirmed by follow-up study.

Results

From July 2010 to June 2013, 31 patients with SH were recruited. Twenty-four (72.7%) of these SH patients exhibited headache fulfilling the TCH criteria. The diagnosis of RCVS was confirmed in 14 (45.2%) of patients with SH and 11 (45.8%) of patients with TCH. Other diagnoses were as follows: primary headaches (SH: 41.9%, TCH: 45.8%) and other secondary causes (SH: 12.9%, TCH: 8.3%). Compared with non-RCVS patients, patients with RCVS were older (50.8 ± 9.3 years vs. 40.8 ± 10.0 years, P = 0.006) and less likely to experience short headache duration of < 1 hour (23.1% vs. 78.6%, P = 0.007). Patients with RCVS were more likely to cite bathing (42.9% vs. 0%, P = 0.004) and less likely to cite exertion (0% vs. 29.4%, P = 0.048) as headache triggers.

Conclusions

Reversible cerebral vasoconstriction syndrome is a common cause of SH and TCH. Considering the potential mortality and morbidity of RCVS, systemic examination of cerebral vessels should be performed in these patients.     

Impact of plasma histones in human sepsis and their contribution to cellular injury and inflammation

Introduction

Circulating histones have been identified as mediators of damage in animal models of sepsis and in patients with trauma-associated lung injury. Despite existing controversies on actual histone concentrations, clinical implications and mechanism of action in various disease conditions, histone levels in human sepsis, association with disease progression and mediated effects on endothelial and immune cells remain unreported. This study aimed to determine histone levels and its clinical implication in septic patients and to elucidate histone-mediated effects ex-vivo.

Methods

Histone levels, endogenous activated protein C (APC) levels and clinical data from two independent cohorts of septic patients were obtained. Histone levels were compared with various control groups including healthy individuals, intensive care unit (ICU) patients without sepsis, ICU patients with multiple organ failure and patients with minor or multiple trauma, all without infection. Endothelial and monocytic cells were stimulated with histones. Cellular integrity and sepsis prototypical cytokines were evaluated. The mechanism of action of histones via Toll-like receptor 4 (TLR4) was evaluated using a function blocking antibody. Histone degradation in plasma was studied by immunoblotting.

Results

Histone H4 levels were significantly elevated in patients with sepsis (cohort I; n = 15 and cohort II; n = 19) versus ICU controls (n = 12), patients with multiple organ failure (n = 12) or minor trauma (n = 7), associated with need for renal replacement therapy and decrease in platelet count during disease progression, and remarkably were significantly associated with increased mortality rates in septic patients (ICU-, 28 day- and 90 day mortality rates). There was an inverse correlation between plasma histones and endogenous APC levels. Histone stimulation induced the release of sepsis prototypic cytokines and decreased cell integrity indicated by a significant increase of lactate dehydrogenase (LDH) and propidium iodide (PI) staining. Blocking of TLR4 decreased cellular cytotoxicity on endothelial cells. The calculated half-life of histones in spiked plasma was 4.6 minutes.

Conclusions

Histone levels in septic patients are significantly increased and might mediate disease aggravation by cellular injury and inflammation via TLR4 signaling, which potentially results in multiple organ failure and fatal outcome.     

The protective effects of a phosphodiesterase 5 inhibitor,sildenafil, on postresuscitation cardiac dysfunction of cardiac arrest: metabolic evidence from microdialysis

Introduction

Recent experimental and clinical studies have indicated the cardioprotective role of sildenafil during ischemia/reperfusion injury. The aim of this study was to determine, by obtaining metabolic evidence from microdialysis, if sildenafil could reduce the severity of postresuscitation myocardial dysfunction and lead to cardioprotection through beneficial effects on energy metabolism.

Methods

Twenty-four male piglets were randomly divided into three groups: sildenafil (n = 8), saline (SA; n = 8) and sham operation (n = 8). Sildenafil pretreatment consisted of 0.5 mg/kg sildenafil administered once intraperitoneally 30 minutes prior to ventricular fibrillation (VF). The myocardial interstitial fluid (ISF) concentrations of glucose, lactate, pyruvate, glutamate and glycerol were determined by microdialysis before VF. Afterward, the piglets were subjected to 8 minutes of untreated VF followed by 15 minutes of open-chest cardiopulmonary resuscitation. ISF was collected continuously, and the experiment was terminated 24 hours after resuscitation.

Results

After 8 minutes of untreated VF, the sildenafil group exhibited higher glucose and pyruvate concentrations of ISF and lower lactate and glutamate levels in comparison with the SA group, and these data reached statistical significance (P < 0.05). Advanced cardiac life support was delivered to both groups, with a 24-hour survival rate showing a promising trend in the sildenafil group (7 of 8 versus 3 of 8 survivors, P < 0.05). Compared with the SA group, the sildenafil group had a better outcome in terms of hemodynamic and oxygen metabolism parameters (P < 0.05). Myocardial tissue analysis revealed a dramatic increase in the contents of ATP, ADP and phosphocreatine in the sildenafil group versus the SA group at 24 hours after return of spontaneous circulation (ROSC; P = 0.03, P = 0.02 and P = 0.02, respectively). Furthermore, 24 hours after ROSC, the sildenafil group had marked elevations in activity of left ventricular Na⁺-K⁺-ATPase and Ca²⁺-ATPase compared with the SA group (P = 0.03, P = 0.04, respectively).

Conclusions

Sildenafil could reduce the severity of postresuscitation myocardial dysfunction, and it produced better clearance of metabolic waste in the ISF. This work might provide insights into the development of a novel strategy to treat postresuscitation myocardial dysfunction.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0641-7) contains supplementary material, which is available to authorized users.