Controversial Issues Concerning Norepinephrine and Intensive Care Following Severe Traumatic Brain Injury

Norepinephrine and corresponding intra- and interorgan pathways are of clinical pathophysiologic and pharmacologic importance as exaggerated activation needs to be reduced and insufficient activation must be supported to prevent further deterioration and therapy-induced organ damage. This is of high relevance in critically ill patients in whom various norepinephrine-influenced organ systems are simultaneousy affected with varying degrees of tolerability and resistance to norepinephrine-induced cell damage and finds its maximal challenge in patients suffering from severe traumatic brain injury (TBI). This comprehensive review describes complex pathophysiologic interactions, including hemodynamic, microcirculatory, hormonal, metabolic, inflammatory, and thrombocytic alterations overshadowed by differential consequences of commonly applied pharmacological interventions following TBI. Overall, investigations published to date suggest that receptor-dependent effects of norepinephrine might predispose to complex evolving deterioration especially during intensive care which is characterized by differentiated complication-driven changes and specific complication-dependent needs. In this context, thrombocytes and leukocytes with their adrenergic receptors and differential norepinephric functional regulation are ideal candidates to influence all organs at once. Despite its secure integration of norepinephrine in clinical routine, future emphasis must be directed at unmasking, monitoring, and controlling possible receptor-mediated detrimental influences which could offset anticipated organ protectio

Treating Intracranial Hypertension in Patients with Severe Traumatic Brain Injury during Neurointensive Care: New Features of Old Problems?

Despite the envisioned breakthrough prophesied for the end of the past century in healing brain injured patients, both clinicians and basic scientists are still struggling with this burden. In the past decades, intensive research has brought forward a plethora of different targets which—in part—have already been integrated in clinical routine directed at detailed monitoring, therapeutic interventions, and prevention of secondary deterioration. While intracellular targets remain obscure alterations on a larger scale as e. g., measured intracranial pressure (ICP), calculated cerebral perfusion pressure (CPP), and various imaging techniques are fundamental components of our present clinical understanding. At bedside, comprehension of pathophysiological loops and circuits of a given value (e. g., ICP) depends on individual knowledge, interpretation, and availability of additional diagnostic steps. As stated in the guidelines brought forward by the American Association of Neurological Surgeons and evaluated in various reports by the Cochrane Library we are still lacking prospective, randomized trials for the majority of the proposed diagnostic and therapeutic interventions. In this context, a recent meta-analysis even questioned the importance of ICP monitoring as we are lacking data from randomized controlled trials clarifying the role of ICP monitoring. The present review is to give an overview of various diagnostic and therapeutic possibilities based on reports published in the past 5 years to strengthen current approaches and nourish future well-designed investigations how to avoid and treat intracranial hypertensio

Early Serum Procalcitonin, Interleukin-6, and 24-Hour Lactate Clearance: Useful Indicators of Septic Infections in Severely Traumatized Patients

Background: Elevated lactate and interleukin-6 (IL-6) levels were shown to correlate with mortality and multiple organ dysfunction in severely traumatized patients. The purpose of this study was to test whether an association exists between 24-hour lactate clearance, IL-6 and procalcitonin (PCT) levels, and the development of infectious complications in trauma patients. Methods: A total of 1757 consecutive trauma patients with an Injury Severity Score (ISS)>16 admitted over a 10-year period were retrospectively analyzed over a 21-day period. Exclusion criteria included death within 72h of admission (24.5%), late admission>12h after injury (16%), and age3days) was 10%. Patients with insufficient 24-hour lactate clearance had a high rate of overall mortality and infections. Elevated early serum procalcitonin on days 1 to 5 after trauma was strongly associated with the subsequent development of sepsis (p<0.01) but not with nonseptic infections. The kinetics of IL-6 were similar to those of PCT but did differentiate between infected and noninfected patients after day 5. Conclusions: This study demonstrates that elevated early procalcitonin and IL-6 levels and inadequate 24-hour lactate clearance help identify trauma patients who develop septic and nonseptic infectious complications. Definition of specific cutoff values and early monitoring of these parameters may help direct early surgical and antibiotic therapy and reduce infectious mortalit

Transcranial color-coded duplex sonography allows to assess cerebral perfusion pressure noninvasively following severe traumatic brain injury

Objective: Assess optimal equation to noninvasively estimate intracranial pressure (eICP) and cerebral perfusion pressure (eCPP) following severe traumatic brain injury (TBI) using transcranial color-coded duplex sonography (TCCDS). Design and setting: This is an observational clinical study in a university hospital. Patients: A total of 45 continuously sedated (BIS  35mmHg), and non-febrile TBI patients. Methods: eICP and eCPP based on TCCDS-derived flow velocities and arterial blood pressure values using three different equations were compared to actually measured ICP and CPP in severe TBI patients subjected to standard treatment. Optimal equation was assessed by Bland-Altman analysis. Results: The equations: $${\hbox{ICP}} = {1}0.{927} \times {\hbox{PI}}\left( {{\hbox{pulsatility}}\,{\hbox{index}}} \right) - {1}.{284}$$ and $${\hbox{CPP}} = {89}.{646} - {8}.{258} \times {\hbox{PI}}$$ resulted in eICP and eCPP similar to actually measured ICP and CPP with eICP 10.6 ± 4.8 vs. ICP 10.3 ± 2.8 and eCPP 81.1 ± 7.9 vs. CPP 80.9 ± 2.1mmHg, respectively. The other two equations, $${\hbox{eCPP}} = \left( {{\hbox{MABP}} \times {\hbox{EDV}}} \right)/{\hbox{mFV}} + {14}$$ and $${\hbox{eCPP}} = \left[ {{\hbox{mFV}}/\left( {{\hbox{mFV}} - {\hbox{EDV}}} \right)} \right] \times \left( {{\hbox{MABP}} - {\hbox{RRdiast}}} \right)$$, resulted in significantly decreased eCPP values: 72.9 ± 10.1 and 67 ± 19.5mmHg, respectively. Superiority of the first equation was confirmed by Bland-Altman revealing a smallest standard deviations for eCPP and eICP. Conclusions: TCCDS-based equation $$\left( {{\hbox{ICP}} = {1}0.{927} \times {\hbox{PI}} - {1}.{284}} \right)$$ allows to screen patients at risk of increased ICP and decreased CPP. However, adequate therapeutic interventions need to be based on continuously determined ICP and CPP value

Model of end stage liver disease (MELD) score greater than 23 predicts length of stay in the ICU but not mortality in liver transplant recipients

INTRODUCTION: The impact of model of end stage liver disease (MELD) score on postoperative morbidity and mortality is still elusive, especially for high MELD. There are reports of poorer patient outcome in transplant candidates with high MELD score, others though report no influence of MELD score on outcome and survival. METHODS: We retrospectively analyzed data of 144 consecutive liver transplant recipients over a 72-month period in our transplant unit, from January 2003 until December 2008 and performed uni- and multivariate analysis for morbidity and mortality, in particular to define the influence of MELD to these parameters. RESULTS: This study identified MELD score greater than 23 as an independent risk factor of morbidity represented by intensive care unit (ICU) stay longer than 10 days (odds ratio 7.0) but in contrast had no negative impact on mortality. Furthermore, we identified transfusion of more than 7 units of red blood cells as independent risk factor for mortality (hazard ratio 7.6) and for prolonged ICU stay (odds ratio [OR] 7.8) together with transfusion of more than 10 units of fresh frozen plasma (OR 11.6). Postoperative renal failure is a strong predictor of morbidity (OR 7.9) and postoperative renal replacement therapy was highly associated with increased mortality (hazard ratio 6.8), as was hepato renal syndrome prior to transplantation (hazard ratio 13.2). CONCLUSIONS: This study identified MELD score greater than 23 as an independent risk factor of morbidity represented by ICU stay longer than 10 days but in contrast had no negative impact on mortality. This finding supports the transplantation of patients with high MELD score but only with knowledge of increased morbidity

Sleep-wake disturbances 6 months after traumatic brain injury: a prospective study

Sleep-wake disturbances (SWD) are common after traumatic brain injury (TBI). In acute TBI, we recently found decreased CSF levels of hypocretin-1, a wake-promoting neurotransmitter. In the present study, we aimed to delineate the frequency and clinical characteristics of post-traumatic SWD, to assess CSF hypocretin-1 levels 6 months after TBI, and to identify risk factors for posttraumatic SWD. A total of 96 consecutive patients were enrolled within the first 4 days after TBI. Six months later, out of 76 TBI patients, who did not die and who did not move to foreign countries, we included 65 patients (86%, 53 males, mean age 39 years) in our study. Patients were examined using interviews, questionnaires, clinical examinations, computed tomography of the brain, laboratory tests (including CSF hypocretin-1 levels, and HLA typing), conventional polysomnography, maintenance of wakefulness and multiple sleep latency tests (MSLT) and actigraphy. Potential causes of post-traumatic SWD were assessed according to international criteria. New-onset sleep-wake disturbances following TBI were found in 47 patients (72%): subjective excessive daytime sleepiness (EDS; defined by the Epworth Sleepiness Scale ≥10) was found in 18 (28%), objective EDS (as defined by mean sleep latency <5 min on MSLT) in 16 (25%), fatigue (daytime tiredness without signs of subjective or objective EDS) in 11 (17%), post-traumatic hypersomnia ‘sensu strictu' (increased sleep need of ≥2 h per 24 h compared to pre-TBI) in 14 (22%) patients and insomnia in 3 patients (5%). In 28 patients (43% of the study population), we could not identify a specific cause of the post-traumatic SWD other than TBI. Low CSF hypocretin-1 levels were found in 4 of 21 patients 6 months after TBI, as compared to 25 of 27 patients in the first days after TBI. Hypocretin levels 6 months after TBI were significantly lower in patients with post-traumatic EDS. There were no associations between post-traumatic SWD and severity or localization of TBI, general clinical outcome, gender, pathological neurological findings and HLA typing. However, post-traumatic SWD correlated with impaired quality of life. These results suggest that sleep-wake disturbances, particularly EDS, fatigue and hypersomnia are common after TBI, and significantly impair quality of life. In almost one out of two patients, post-traumatic SWD appear to be directly related to the TBI. An involvement of the hypocretin system in the pathophysiology of post-traumatic SWD appears possible. Other risk factors predisposing towards the development of post-traumatic SWD were not identifie

V.A.C.® Abdominal Dressing System: A Temporary Closure for Open Abdomen

Background and Purpose:: The study reports experience with the recently commercially available V.A.C.® Abdominal Dressing System, a system designed for a temporary closure of an open abdomen situation under negative pressure. The method allows a late primary fascial closure after laparotomy in case of damage control, abdominal compartment syndrome or severe intra-abdominal spesis and facilitates delayed reconstruction of a large ventral hernia. Patients and Methods:: 18 patients with an open abdomen after laparotomy were managed between February 2002 and September 2004. Results:: Twelve patients after primary, one patient after secondary fascial closure and one patient with partially primary closure and resorbable mesh for abdominal wall reconstruction were free of wound infection or dehiscence of the abdominal wall. Evisceration or enteric fistulas were not observed. Five patients died in consequence of severe injury, a multiple organ failure or septic complications. Conclusion:: V.A.C.® Abdominal Dressing System is an effective temporary closure technique for open abdomen in critically ill patients which makes a late primary fascial closure up to 2 months after initial laparotomy possible either in trauma patients or in case of severe intraabdominal infection. The technique is simple and easily mastere

Base excess determined within one hour of admission predicts mortality in patients with severe pelvic fractures and severe hemorrhagic shock

Abstract : Background: : Unstable pelvic ring fractures with exsanguinating hemorrhages are rare but potentially lifethreatening injuries. The aim of this retrospective study was to evaluate whether early changes in acid- base parameters predict mortality of patients with severe pelvic trauma and hemorrhagic shock. Methods: : Data for 50 patients with pelvic ring disruption and severe hemorrhage were analyzed retrospectively. In all patients, the pelvic ring was temporarily stabilized by C-clamp. Patients with ongoing bleeding underwent laparotomy with extra and/or intraperitoneal pelvic packing, as required. Base excess, lactate, and pH were measured upon admission and at 1, 2, 3, 4, 6, 8, and 12 h postadmission. Patients were categorized as early survivors (surviving the first 12 h after admission) and nonsurvivors. Statistical analysis was performed by Mann-Whitney test; significance was assumed at p < 0.05. Receiver operating characteristic curves were generated for early mortality from each acid-base variable. Results: : Sixteen patients (32%) were nonsurvivors due to hemorrhagic shock (n = 13) or severe traumatic brain injury (n = 3). Thirty-four patients were early survivors. Base excess, lactate, and pH significantly discriminated between early survivors and nonsurvivors. Base excess determined 1 h after admission discriminated most strongly, with an area under the receiver operating characteristic curve of 0.915 (95% confidence interval, 0.836-0.993; p < 0.001). Conclusion: : Base excess, lactate, and pH discriminate early survivors from nonsurvivors suffering from severe pelvic trauma and hemorrhagic shock. Base excess measured 1 h after admission best predicted early mortality following pelvic trauma with concomitant hemorrhag

Thromboelastography to Monitor Clotting/Bleeding Complications in Patients Treated with the Molecular Adsorbent Recirculating System

Background. The Molecular Adsorbent Recirculating System (MARS) has been shown to clear albumin-bound toxins from patients with liver failure but might cause bleeding complications potentially obscuring survival benefits. We hypothesized that monitoring clotting parameters and bed-side thromboelastography allows to reduce bleeding complications. Methods. Retrospective analysis of 25 MARS sessions during which clotting parameters were monitored by a standardized protocol. Results. During MARS therapy median INR increased significantly from 1.7 to 1.9 platelet count and fibrinogen content decreased significantly from 57 fL−1 to 42 fL−1 and 2.1 g/L to 1.5 g/L. Nine relevant complications occurred: the MARS system clotted 6 times 3 times we observed hemorrhages. Absent thrombocytopenia and elevated plasma fibrinogen predicted clotting of the MARS system (ROC 0.94 and 0.82). Fibrinolysis, detected by thromboelastography, uniquely predicted bleeding events. Conclusion. Bed-side thromboelastography and close monitoring of coagulation parameters can predict and, therefore, help prevent bleeding complications during MARS therapy

Two different hematocrit detection methods: Different methods, different results?

BACKGROUND: Less is known about the influence of hematocrit detection methodology on transfusion triggers. Therefore, the aim of the present study was to compare two different hematocrit-assessing methods. In a total of 50 critically ill patients hematocrit was analyzed using (1) blood gas analyzer (ABLflex 800) and (2) the central laboratory method (ADVIA(R) 2120) and compared. FINDINGS: Bland-Altman analysis for repeated measurements showed a good correlation with a bias of +1.39% and 2 SD of +/- 3.12%. The 24%-hematocrit-group showed a correlation of r2 = 0.87. With a kappa of 0.56, 22.7% of the cases would have been transfused differently. In the-28%-hematocrit group with a similar correlation (r2 = 0.8) and a kappa of 0.58, 21% of the cases would have been transfused differently. CONCLUSIONS: Despite a good agreement between the two methods used to determine hematocrit in clinical routine, the calculated difference of 1.4% might substantially influence transfusion triggers depending on the employed method