Ultrasonography of the optic nerve sheath may be useful for detecting raised intracranial pressure after severe brain injury

Objective To assess at admission to the ICU the relationship between optic nerve sheath diameter (ONSD) and intracranial pressure (ICP) and to investigate whether increased ONSD at patient admission is associated with raised ICP in the first 48 h after trauma. Design and setting Prospective, blind, observational study in a surgical critical care unit, level 1 trauma center. Patients and participants 31 adult patients with severe traumatic brain injury (TBI; Glasgow coma scale ≤ 8) requiring sedation and ICP monitoring, and 31 control patients without brain injury requiring sedation. Measurements and results ONSD was measured with a 7.5-MHz linear ultrasound probe. Two TBI groups were defined on the basis of ICP profile. If ICP exceeded 20 mmHg for more than 30 min in the first 48 h (before any specific treatment), patients were considered to have high ICP; if not, they had normal ICP. The largest ONSD value (the highest value for the right and left eye) was significantly higher in high ICP patients (6.3 ± 0.6 vs. 5.1 ± 0.7 mm in normal ICP patients and 4.9 ± 0.3 mm in control patients). There was a significant relationship between the largest ONSD and ICP at admission (r = 0.68). The largest ONSD was a suitable predictor of high ICP (area under ROC curve 0.96). When ONSD was under 5.7 mm, the sensitivity and negative predictive values for high ICP were 100%. Conclusions In the early posttraumatic period, ocular ultrasound scans may be useful for detecting high ICP after severe TBI. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. This article is discussed in the editorial available at: .     

Refractory intracranial hypertension and “second-tier” therapies in traumatic brain injury

Objective To quantify the occurrence of high intracranial pressure (HICP) refractory to conventional medical therapy after traumatic brain injury (TBI) and to describe the use of more aggressive therapies (profound hyperventilation, barbiturates, decompressive craniectomy). Design Prospective study of 407 consecutive TBI patients Setting Three neurosurgical intensive care units (ICU). Measurements and results Intracranial pressure (ICP) was studied during the first week after TBI; 153 patients had at least 1 day of ICP > 20 mmHg. Early surgery was necessary for 221 cases, and standard medical therapy [sedation, mannitol, cerebrospinal fluid (CSF) withdrawal, PaCO₂ 30–35 mmHg] was used in 135 patients. Reinforced treatment (PaCO₂ 25–29 mmHg, induced arterial hypertension, muscle relaxants) was used in 179 cases (44%), and second-tier therapies in 80 (20%). Surgical decompression and/or barbiturates were used in 28 of 407 cases (7%). Six-month outcome was recorded in 367 cases using the Glasgow outcome scale (GOS). The outcome was favorable (good recovery or moderate disability) in 195 cases (53%) and unfavorable (all the other categories) in 172 (47%). HICP was associated with worse outcome. Outcome for cases who had received second-tier therapies was significantly worse (43% favorable at 6 months, p = 0.03). Conclusions HICP is frequent and is associated with worse outcome. ICP was controlled by early surgery and first-tier therapies in the majority of cases. Profound hyperventilation, surgical decompression and barbiturates were used in various combinations in a minority of cases. The indications for surgical decompression and/or barbiturates seem restricted to less than 10% of severe TBI.     

Predicting outcome after severe traumatic brain injury using the serum S100B biomarker: Results using a single (24 h) time-point

Background and objectives

In recent years, biochemical markers have been employed to predict the outcome of patients with traumatic brain injury (TBI). In mild TBI, S100B has shown the most promise as a marker of outcome. The objective of this study in patients with severe TBI was to: show the range of serum S100B levels during the acute phase after trauma: determine if S100B has potential to discriminate favourable from unfavourable outcome in patients with similar brain injury severity scores and to establish an S100B ‘cut-off’ predictive for death.

Methods

All patients with severe TBI, admitted to this neurointensive care unit within 24 h of injury were eligible for inclusion in the study. One serum blood sample was obtained from each patient at the 24 h post-injury time-point. S100B levels were measured using enzyme-linked immunosorbent assay. Injuries were coded using an internationally recognised injury severity scoring system (ISS). Three-month follow-up was undertaken with outcome assessed using the Glasgow outcome score (GOS).

Results

One hundred patients were recruited. Serum S100B levels ranged from 0.08 to 12.62 μg L⁻¹ S100B levels were significantly higher in patients with a GOS of 1 (death) 2 and 3 (unfavourable outcome) compared with those with GOS 4 and 5 (good recovery). In this study a cut-off point of 0.53 μg L⁻¹ has sensitivity of >80% and specificity of 60% to predict unfavourable outcome and 49% to predict death.

Conclusion

In 100 patients studied with similar brain injury severity scores, serum S100B measured at the 24-h time-point after injury is significantly associated with outcome but a cut-off 0.53 μg L⁻¹ does not have good prognostic performance.     

Posttraumatic brain vulnerability to hypoxia-hypotension: the importance of the delay between brain trauma and secondary insult

Objective To examine whether the effect of hypoxia-hypotension (HH) after traumatic brain injury (TBI) is affected by the delay between insults. Design Thirty Sprague-Dawley rats were randomized into five groups: sham, TBI alone (trauma alone, impact-acceleration, 450 g weight drop from 1.8 m), HH alone (blood depletion, mean arterial pressure 40 mmHg, FIO₂ = 10%, 15 min), TBI + early HH (TBI followed by HH, 45-min delay), and TBI + late HH (225-min delay). Cerebral perfusion pressure was continuously recorded. Brain microdialysis and PtiO₂ probes were inserted stereotaxically into the right thalamus. Measurements and results After the HH period and for 60 min a significant increase in cerebral lactate-pyruvate ratio was observed in groups subjected to HH vs. TBI alone and sham groups (33.0 ± 5.1 for HH alone and 51.9 ± 6.7 for TBI + early HH vs. 16.7 ± 2.4 for TBI alone at the same time, 27.6 ± 4.4 for TBI + late HH vs. 13.1 ± 1 for TBI alone at the same time). There was no significant difference in lactate-pyruvate ratio peaks between HH alone and TBI + late HH while it was higher in TBI + early HH. Similar results were obtained for cerebral glycerol. PtiO₂ during HH phase did not differ between HH alone, TBI + early HH and TBI + late HH (respectively, 4.2 ± 3.1, 4.9 ± 5.7, and 2.9 ± 1.8 mmHg). Conclusions A 45-min delay between HH and TBI has important metabolic consequences while a 225-min delay has a similar effect as HH in a noninjured brain. The posttraumatic brain vulnerability to HH depends on the delay between cerebral aggressions. This article is discussed in the editorial available at: .     

Intracranial pressure complicating severe traumatic brain injury in children: monitoring and management

Objective To identify factors associated with the use of intracranial pressure (ICP) monitoring and to establish which ICP-targetted therapies are being used in children with severe traumatic brain injury (TBI) in the United Kingdom. To evaluate current practice against recently published guidelines.Design and setting Prospective data collection of clinical and demographic information from paediatric and adult intensive care units in the UK and Ireland admitting children (< 16 years) with TBI between February 2001 and August 2003.Results Detailed clinical information was obtained for 501 children, with information on the use of ICP monitoring available in 445. ICP monitoring was used in only 59% (75/127) of children presenting with an emergency room Glasgow Coma Scale of 8 or below. Large between centre variation was seen in the use of ICP monitoring, independent of severity of injury. There were 86 children who received ICP-targetted therapies without ICP monitoring. Wide between centre variation was found in the use of ICP-targetted therapies and in general aspects of management, such as fluid restriction, the use of muscle relaxants and prophylactic anticonvulsants. Intra-ventricular catheters are rarely placed (6% of cases); therefore cerebrospinal fluid drainage is seldom used as a first-line therapy for raised ICP. Jugular venous bulb oximetry (4%), brain microdialysis (< 1%) and brain tissue oxygen monitoring (< 1%) are rarely used in current practice. Contrary to published guidelines, moderate to severe hyperventilation is being used without monitoring for cerebral ischaemia.Conclusions There is an urgent need for greater standardisation of practice across UK centres admitting children with severe TBI.This study was supported by grants from the Paediatric Intensive Care Society, Birmingham Children's Hospital Research Foundation and the Warwick University Research and Teaching Development Fund.     

重型颅脑损伤患者血浆S-100B蛋白测定的临床意义

目的　探讨血浆 S 10 0 B蛋白作为一种生物学指标在重型颅脑损伤诊断及预后判断中的应用价值。方法　重型颅脑损伤患者 6 6例 ,伤后早期 (2～ 6 h)抽取血浆标本 ,并从伤后 2 4 h起连续 3～ 7d检测血浆 S 10 0 B蛋白含量 ,将其结果与患者伤后 6个月格拉斯哥预后评分 (GOS)进行比较。结果　 6 6例患者中死亡 2 5例 ,致残 2 2例 ,良好 19例。死亡组 S 10 0 B平均 2 .6 0 μg/ L,明显高于存活组 (0 .5 5 μg/ L,P<0 .0 0 1) ;死亡组中有 14例 S 10 0 B峰值超过 2 .0 0 μg/ L,而存活组中只有 4例峰值超过 2 .0 0 μg/ L(P<0 .0 0 5 )。结论　血浆 S 10 0 B蛋白在重型颅脑损伤的诊断及预后判断中具有可靠的应用价值。     

Monitoring brain tissue oxygen tension in brain-injured patients reveals hypoxic episodes in normal-appearing and in peri-focal tissue

Objective We compared brain tissue oxygen tension (PtiO₂) measured in peri-focal and in normal-appearing brain parenchyma on computerized tomography (CT) in patients following traumatic brain injury (TBI). Design Prospective observational study. Setting Neurointensive care unit. Patients and participants Thirty-two consecutive TBI patients were subjected to PtiO₂ monitoring. Interventions Peri-focal tissue was identified by the presence of a hypodense area of the contusion and/or within 1 cm from the core of the contusion. The position of the tip of the PtiO₂ probe was assessed at follow-up CT scan. Measurements and results Mean PtiO₂ in the peri-contusional tissue was 19.7 ± 2.1 mmHg and was lower than PtiO₂ in normal-appearing tissue (25.5 ± 1.5 mmHg, p < 0.05), despite a greater cerebral perfusion pressure (CPP) (73.7 ± 2.3 mmHg vs. 67.4 ± 1.4 mmHg, p < 0.05). We observed both in peri-focal tissue and in normal-appearing tissue episodes of brain hypoxia (PtiO₂ < 20 mmHg for at least 10 min), whose median duration was longer in peri-focal tissue than in normal-appearing tissue (51% vs. 34% of monitoring time, p < 0.01). In peri-focal tissue, we observed a progressive PtiO₂ increase from pathologic to normal values (p < 0.01). Conclusions Multiple episodes of brain hypoxia occurred over the first 5 days following severe TBI. PtiO₂ was lower in peri-contusional tissue than in normal-appearing tissue. In peri-contusional tissue, a progressive increase of PtiO₂ from pathologic to normal values was observed over time, suggestive of an improvement at microcirculatory level.     

血清S100B检测对创伤性脑损伤的诊断价值

目的 探讨血清S100钙结合蛋白B(S100B)在判断创伤性脑损伤(TBI)患者病情严重程度和预后评估中的应用价值.方法 选取该院救治的106例TBI患者,分别于伤后第1、3、5天检测血清S100B的水平;根据入院时的格拉斯哥昏迷评分(GCS)分为3组:轻度组65例、中度组14例、重度组27例;按照3个月时回访的格拉斯...     

Transfusion of erythrocyte concentrates produces a variable increment on cerebral oxygenation in patients with severe traumatic brain injury

Objective To investigate the long-term influence of erythrocyte transfusion on cerebral oxygenation in patients with severe traumatic brain injury.Design Prospective and observational study.Setting Neurotrauma intensive care unit of trauma center level I.Patients Sixty consecutive, hemodynamically stable patients with severe traumatic brain injury, pretransfusion hemoglobin < 100 g/l, non-bleeding and monitored through intracranial pressure and brain tissue partial pressure of oxygen (PtiO₂) catheters were included.Interventions Transfusion of 1–2 units of red blood cells.Measurements and results Ten sets of variables (pretransfusion, end of transfusion, and 1, 2, 3, 4, 5, 6, 12 and 24 h after transfusion) were recorded, including: PtiO₂, cerebral perfusion pressure (CPP), end-tidal CO₂, peripheral saturation of oxygen, temperature, hemoglobin, lactate and PaO₂/FiO₂ ratio. Transfusion was associated with an increase in PtiO₂ during a 6-h period, with a peak at 3 h (26.2%; p = 0.0001) in 78.3% of the patients. No relationship was observed between PtiO₂, CPP and hemoglobin increments. The relative increment in PtiO₂ at hour 3 was only correlated with baseline PtiO₂ (r² 0.166; p = 0.001). All of the patients with basal PtiO₂ < 15 mmHg showed an increment in PtiO₂ versus 74.5% of patients with basal PtiO₂ ≥ 15 mmHg (p < 0.01, hour 3).Conclusions Erythrocyte transfusion is associated with a variable and prolonged increment of cerebral tissue oxygenation in anemic patients with severe traumatic brain injury. Low baseline PtiO₂ levels (< 15 mmHg) could define those patients who benefit the most from erythrocyte transfusion.     

Post-traumatic headache: facts and doubts

The International Classification of Headache Disorders does not separate the moderate from severe/very severe traumatic brain injury (TBI), since they are all defined by Glasgow coma scale (GCS) < 13. The distinction between the severe and very severe TBI (GCS < 8) should be made upon coma duration that in the latter may be longer than 15 days up to months in the case of vegetative state. Post-traumatic amnesia duration may double the coma duration itself. Therefore, the 3-month parameter proposed to define the occurrence or resolution of post-traumatic headache (PTH) appears inadequate. Following TBI, neuropathic pain, central pain, thalamic pain, combined pain are all possible and they call for proper pharmacological approaches. One more reason for having difficulties in obtaining information about headache in the early phase after regaining consciousness is the presence of concomitant medications that may affect pain perception. Post-traumatic stress disorder (PTSD) develops days or weeks after stress and tends to improve or disappear within 3 months after exposure; interestingly, this spontaneous timing resembles that of PTH. In our experience the number of TBI patients with PTH at 1-year follow-up is lower in those with longer coma duration and more severe TBI. Cognitive functioning evaluated after at least 12 months from TBI, showed mild or no impairment in these patients with severe TBI and PTH, whereas they have psychopathological changes, namely anxiety and depression. The majority of patients with PTH after severe/very severe TBI had skull fractures or dural lacerations and paroxystic EEG abnormalities. The combination of psychological changes (depression and anxiety) and organic features (skull fractures, dural lacerations, epileptic EEG abnormalities) in PTH may be inversely correlated with the severity of TBI, with prevalence of psychological disturbances in mild TBI and of organic lesions in severe TBI. On the other hand, only in severe TBI patients with good cognitive recovery the influence of the psychopathological disorders may play a role. In fact, the affective pain perception is probably related to the integrity of cognitive functions as in mild TBI and in severe TBI with good cognitive outcome.     

Role of serum S100B as a predictive marker of fatal outcome following isolated severe head injury or multitrauma in males.

BACKGROUND: Severe traumatic brain injury (TBI) is associated with a 30%-70% mortality rate. S100B has been proposed as a biomarker for indicating outcome after TBI. Nevertheless, controversy has arisen concerning the predictive value of S100B for severe TBI in the context of multitrauma. Therefore, our aim was to determine whether S100B serum levels correlate with primary outcome following isolated severe TBI or multitrauma in males. METHODS: Twenty-three consecutive male patients (age 18-65 years), victims of severe TBI [Glasgow Coma Scale (GCS) 3-8] (10 isolated TBI and 13 multitrauma with TBI) and a control group consisting of eight healthy volunteers were enrolled in this prospective study. Clinical outcome variables of severe TBI comprised: survival, time to intensive care unit (ICU) discharge, and neurological assessment [Glasgow Outcome Scale (GOS) at ICU discharge]. Venous blood samples were taken at admission in the ICU (study entry), 24 h later, and 7 days later. Serum S100B concentration was measured by an immunoluminometric assay. RESULTS: At study entry (mean time 10.9 h after injury), mean S100B concentrations were significantly increased in the patient with TBI (1.448 microg/L) compared with the control group (0.037 microg/L) and patients with fatal outcome had higher mean S100B (2.10 microg/L) concentrations when compared with survivors (0.85 microg/L). In fact, there was a significant correlation between higher initial S100B concentrations and fatal outcome (Spearman's =0.485, p=0.019). However, there was no correlation between higher S100B concentrations and the presence of multitrauma. The specificity of S100B in predicting mortality according to the cut-off of 0.79 microg/L was 73% at study entry. Conclusions: Increased serum S100B levels constitute a valid predictor of unfavourable outcome in severe TBI, regardless of the presence of associated multitrauma.     

脑脊液S100钙结合蛋白B在创伤性颅脑损伤中应用研究

目的 探讨脑脊液S100钙结合蛋白B(S100B)在评估创伤性颅脑损伤(TBI)严重程度和预后中的价值.方法 选取自2017年10月至2019年6月苏州大学附属常熟医院收治的43例TBI患者为研究对象,根据格拉斯哥结局量表分为预后良好组(n=20)与预后不良组(n=23).通过脑室外引流获取脑脊液,测定患者术后6、12...     

The effects of sleep on the relationship between brain injury severity and recovery of cognitive function: A prospective study

Background

Disturbed sleep pattern is a common symptom after head trauma and its prevalence in acute traumatic brain injury (TBI) is less discussed. Sleep has a profound impact on cognitive function recovery and the mediating effect of disturbed sleep on cognitive function recovery has not been examined after acute TBI.

Objectives

To identify the prevalence of disturbed sleep in mild, moderate, and severe acute TBI patients, and to determine the mediating effects of sleep on the relationship between brain injury severity and the recovery of cognitive function.

Design

A prospective study design.

Setting

Neurosurgical wards in a medical center in northern Taiwan.

Participants

Fifty-two acute TBI patients between the ages of 18 and 65 years who had received a diagnosis of TBI for the first time, and were admitted to the neurosurgical ward.

Method

The severity of brain injury was initially determined using the Glasgow Coma Scale. Each patient wore an actigraphy instrument on a non-paralytic or non-dominated limb for 7 consecutive days. A 7-day sleep diary was used to facilitate data analysis. Cognitive function was assessed on the first and seventh day after admission based on the Rancho Los Amigos Levels of Cognitive Functioning.

Results

The mild (n = 35), moderate (n = 7) and severe (n = 10) TBI patients exhibited poorer sleep efficiency, and longer total sleep time (TST) and waking time after sleep onset, compared with the normative values for the sleep-related variables (P < .05 for all). The severe and moderate TBI patients had longer daytime TST than the mild TBI patients (P < .001), and the severe TBI patients had longer 24-h TST than the mild TBI patients (P = .001). The relationship between the severity of brain injury and the recovery of cognition function was mediated by daytime TST (t = −2.65, P = .004).

Conclusions

Poor sleep efficiency, prolonged periods of daytime sleep, and a high prevalence of hypersomnia are common symptoms in acute TBI patients. The duration of daytime sleep mediates the relationship between the severity of brain injury and the recovery of cognition function.     

The association between field Glasgow Coma Scale score and outcome in patients undergoing paramedic rapid sequence intubation

Early intubation is standard for treating severe traumatic brain injury (TBI). Aeromedical crews and select paramedic agencies use rapid sequence intubation (RSI) to facilitate intubation after TBI, with Glasgow Coma Scale (GCS) score commonly used as a screening tool. To explore the association between paramedic GCS and outcome in patients with TBI undergoing prehospital RSI, paramedics prospectively enrolled adult major trauma victims with GCS 3–8 and clinical suspicion for head trauma to undergo succinylcholine-assisted intubation as part of the San Diego Paramedic RSI Trial. The following data were abstracted from paramedic debriefing interviews and the county trauma registry: demographics, mechanism, vital signs including GCS score, clinical evidence of aspiration before RSI, arrival laboratory values, hospital course, and outcome. Paramedic GCS calculations were confirmed during debriefing interviews. Patients were stratified by GCS score, with chi-square and receiver-operator-curve (ROC) analysis used to explore the relationship between GCS and hypoxia, head injury severity, aspiration, intensive care unit (ICU) length of stay, and outcome. Cohort analysis was used to explore potential reasons for early extubation and discharge from the ICU in some patients. A total of 412 patients were included in this analysis. A total of 81 patients (20%) were extubated and discharged from the ICU in 48 h or less; these patients had higher pre-RSI oxygen saturation (SaO₂) values and higher arrival serum ethanol levels. Paramedic and physician GCS calculations had high agreement (kappa = 0.995). A statistically significant relationship was observed between GCS score and Head Abbreviated Injury Score (AIS), survival, and pre-RSI SaO₂ values. However, ROC analysis revealed a limited ability of GCS to predict the presence of severe TBI, injury severity, desaturation, aspiration, ICU length of stay, or ultimate survival. In conclusion, paramedics seem to accurately calculate GCS values before prehospital RSI. Although a relationship between paramedic GCS and outcome exists, the ability to predict the severity of injury, airway-related complications, ICU length of stay, and overall survival is limited using this single variable. Other factors should be considered to screen TBI patients for prehospital RSI.     

Relationship between injury severity and serum tau protein levels in traumatic brain injured rats

Background

Although serum tau protein levels increase following TBI, the time course is unknown. The aim of the present study was to determine whether serum tau protein levels increased in both a severity-dependent and time-dependent manner in an experimental model of rat traumatic brain injury (TBI).

Methods

A total of 24 Sprague-Dawley rats were subjected to varying grades of TBI using a contusion injury model on the right parietal cortex. Enzyme-linked Immunoabsorbent Assay (ELISA) analysis for serum was performed at 15 min pre-injury, 1, 6, 24, 48, and 168 h post-injury. Immunoblotting for serum tau protein, neurological evaluation and histological observation were also performed.

Results

Tau protein levels rapidly increased after 1 h in both mild and severe TBI groups (p < 0.001), and declined after 6 h. In the sham-operated group, tau protein levels did not change significantly after TBI. Tau protein levels were severity-dependent at 1 and 6 h after TBI. The levels were higher in the severe TBI group than in the mild TBI group at 1 h (p < 0.001) and 6 h (p < 0.001).

Conclusions

Serum tau protein levels were severity-dependent and time-dependent at 1 and 6 h after TBI. However, the serum tau protein may not be a useful marker 24 h after TBI.     

Respiratory mechanics in brain-damaged patients

Objective To assess respiratory mechanics on the 1st and 5th days of mechanical ventilation in a cohort of brain-damaged patients on positive end-expiratory pressure (PEEP) of 8 cmH₂O or zero PEEP (ZEEP).Design and setting Physiological study with randomized control trial design in a multidisciplinary intensive care unit of a university hospital.Patients and measurements Twenty-one consecutive mechanically ventilated patients with severe brain damage and no acute lung injury were randomly assigned to be ventilated with ZEEP (n = 10) or with 8 cmH₂O of PEEP (n = 11). Respiratory mechanics and arterial blood gases were assessed on days 1 and day 5 of mechanical ventilation.Results In the ZEEP group on day 1 static elastance and minimal resistance were above normal limits (18.9 ± 3.8 cmH₂O/l and 5.6 ± 2.2 cmH₂O/l per second, respectively); on day 5 static elastance and iso-CO₂ minimal resistance values were higher than on day 1 (21.2 ± 4.1 cmH₂O/l; 7.0 ± 1.9 cmH₂O/l per second, respectively). In the PEEP group these parameters did not change significantly. One of the ten patients on ZEEP developed acute lung injury. On day 5 there was a significant decrease in PaO₂/FIO₂ in both groups.Conclusions On day 1 of mechanical ventilation patients with brain damage exhibit abnormal respiratory mechanics. After 5 days of mechanical ventilation on ZEEP static elastance and minimal resistance increased significantly, perhaps reflecting “low lung volume” injury. Both could be prevented by administration of moderate levels of PEEP.This work was supported by the Thorax foundation.This article is discussed in the editorial available at:     

The effect of exogenous surfactant in patients with lung contusions and acute lung injury

Objective To investigate the acute effect of surfactant replacement in multiple-trauma patients with lung contusion and acute lung injury. Design and setting Prospective randomized clinical trial in the 14-bed ICU of a 750-bed university hospital. Patients and participants Sixteen ventilated trauma patients with severe refractory hypoxemia (PaO₂/FIO₂ < 150 mmHg) and lung contusions. Interventions Patients were randomly assigned to either surfactant administration (n = 8) or standard treatment (n = 8). A single dose of natural bovine surfactant was instilled bronchoscopically in the involved lung areas; each segmental bronchus received (200/19) mg/kg body weight. Measurements and results The surfactant group demonstrated an acute improvement in oxygenation after surfactant replacement compared both to control group and to baseline values. In the surfactant group PaO₂/FIO₂ increased from 100 ± 20 mmHg at baseline to 140 ± 20 (6 h), 163 ± 26 (12 h), and 187 ± 30 mmHg (24 h). Compliance increased from 30 to 36 ml/cmH₂O at 6 h after administration, and this increase remained significant at the 24, 48, and 72 h time points. The surfactant group demonstrated a higher response to recruitment maneuvers than the control group at 6 h. The mean duration of ventilatory support was 5.6 ± 2.6 days in the surfactant group and 8.1 ± 2.4 days in the control group. Conclusions Surfactant replacement was well tolerated in patients with lung contusions and severe hypoxemia and resulted in improved oxygenation and compliance.     

Transcranial Doppler ultrasound goal-directed therapy for the early management of severe traumatic brain injury

Objective To evaluate the usefulness of early transcranial Doppler ultrasound (TCD) goal-directed therapy after severe traumatic brain injury initiated before invasive cerebral monitoring is available. Design Prospective, observational clinical study. Setting Surgical intensive care unit, university hospital. Patients and participants Twenty-four severely brain-injured patients. Interventions All patients had TCD measurements immediately on admission (T0) and when invasive cerebral monitoring was available (T1). TCD was considered abnormal when two out of three measured values were outside the following limits: Vm < 30 cm/s, Vd < 20 cm/s, PI  > 1.4. When admission TCD was abnormal, attending physicians modified treatment to increase cerebral perfusion pressure. Measurements and results Admission TCD was performed 18 ± 11 min (T0) after admission, whereas cerebral inasive monitoring was available 242 ± 116 min (T1) after admission. At T0, 11 (46%) patients had abnormal TCD values (group 1) and 13 had normal TCD values (group 2); mean arterial pressure was comparable between groups. All group 1 patients received mannitol and/or norepinephrine. At T1, mean arterial pressure was increased compared to admission in group 1 (105 ± 17 mmHg vs. 89 ± 15 mmHg, p < 0.05) and only two patients had still an abnormal TCD. Although group 1 patients had higher intracranial pressure than those of group 2 (32 ± 13 mmHg vs. 22 ± 10 mmHg, p < 0.01), both cerebral perfusion pressure and jugular venous oxygen saturation were comparable between the groups. Conclusions The use of TCD at hospital admission allows identification of severely brain-injured patients with brain hypoperfusion. In such high-risk patients, early TCD goal-directed therapy can restore normal cerebral perfusion and might then potentially help in reducing the extent of secondary brain injury.     

Short-term beneficial effects of methylene blue on kidney damage in septic shock patients

Objective We previously demonstrated that upregulation of renal inducible nitric oxide synthase (iNOS) is associated with proximal tubule injury during systemic inflammation in humans. In this study we investigated the short-term effect of methylene blue (MB), an inhibitor of the NO pathway, on kidney damage and function in septic shock patients. Design and setting A prospective clinical study conducted in an intensive care unit. Patients Nine patients (four men, five women, mean age 71 ± 3 years) with confirmed or suspected bacterial infection and with refractory septic shock defined as a mean arterial pressure ≤ 70 mmHg despite norepinephrine infusion ≥ 0.2 μg/kg per minute. Interventions A 4 h continuous intravenous infusion of 1 mg/kg MB per hour. Measurements and results The urinary excretion of NO metabolites decreased with median 90% (range 75–95%) from baseline to 6 h after MB administration. The first 24 h creatinine clearance improved by 51% (18–173%) after MB treatment but was still strongly impaired. During the first 6 h after the start of MB treatment both the urinary excretion of cytosolic glutathione S-transferase A1-1 and P1-1, markers for proximal and distal tubule damage, respectively, decreased by 45% (10–70%) and 70% (40–85) vs. baseline. After termination of the MB infusion the NO metabolites and markers of tubular injury returned to pretreatment levels. Conclusions In septic patients with refractory shock short-term infusion of MB is associated with a decrease in NO production and an attenuation of the urinary excretion of renal tubular injury markers. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. S. H. was supported by a grant from The Netherlands Organization for Scientific Research; F. v. H. was supported by a grant from the Waikato Medical Research Foundation; P. P. is recipient of a Clinical Fellowship grant of The Netherlands Organization for Scientific Research.     

Association of statin therapy and increased survival in patients with multiple organ dysfunction syndrome

Objective The multiple organ dysfunction syndrome (MODS) is the sequential failure of several organ systems after a trigger event, such as sepsis, pneumonia or cardiogenic shock. Even today, mortality is high. Statin therapy is associated with reduction of inflammation and subsequent rates of severe sepsis and ICU admission of patients admitted to hospital with presumed or documented acute bacterial infection. Our study aimed to characterize a potential survival benefit by statin therapy in MODS patients.Design Retrospective cohort study.Setting Twelve-bed medical intensive care unit in a university center.Patients Forty score-defined MODS patients under statin treatment and 80 age- and sex-matched score-defined MODS patients without statin treatment. Inclusion criterion was an APACHE II score ≥ 20 at admission to ICU.Interventions Assessment of statin treatment and calculation of disease severity by scoring. The patients were followed up for 28-day mortality as well as for hospital mortality.Measurements and results The MODS severity was equally pronounced in both groups. There were 42/80 deaths in the group without statin treatment and 13/40 deaths in the statin group (28-day mortality 53% vs. 33%, p = 0.03). Cox proportional hazard analysis revealed a hazard ratio of 0.53 (95% CI 0.29–0.99, p = 0.04). Hospital mortality was calculated at 72% (non-statin group) vs. 35% (statin group; chi-square  = 15.6, p < 0.0001). The overall hospital mortality was 60%.Conclusions Patients under statin treatment developing MODS might have a better outcome than patients without statin therapy, probably by reduction of inflammatory responses and increase of vagal activity in MODS.H.S. and U.M.-W. are supported by a grant of the Deutsche Forschungsgemeinschaft (SCHM 1398/3-1,-2). M.B. is supported by a grant of the Deutsche Forschungsgemeinschaft (BU 859/3-1,-2,3). There was no involvement of the founding source in study design, analysis and interpretation of the data, in writing the report and in the decision to submit the paper for publication. There is no conflict of interest inherent in the paper's content.