Reto Stocker

Incidence and clinical pattern of the abdominal compartment syndrome after "damage-control" laparotomy in 311 patients with severe abdominal and/or pelvic trauma.

Objective To investigate the incidence, main physiologic effects, and therapeutic management of the abdominal compartment syndrome (ACS) after severe abdominal and/or pelvic trauma. Design Retrospective analysis from January 1991 to December 1996; prospective study from January 1997 to August 1998. Setting Level I trauma center, intensive care unit. Patients A total of 311 patients with severe abdominal and/or pelvic trauma and “damage-control” laparotomy on day of admission. Interventions The ACS was defined as the development of significant respiratory compromise, including elevated inspiratory pressure of >35 mbar, a decreased Horowitz quotient (<150 torr [<20 kPa]), renal dysfunction (urine output, <30 mL/hr), hemodynamic instability necessitating catecholamines, and a rigid or tense abdomen. Beginning with January 1997, urinary bladder pressure as an additional variable for the diagnosis of ACS was continuously measured in patients (n = 12) at risk. Bladder pressures of >25 mm Hg indicated ACS. Measurements and Main Results Seventeen patients (5.5%) developed ACS because of persistent intra-abdominal/retroperitoneal bleeding (n = 12; 70.6%) or visceral edema (n = 5; 29.4%). All patients with ACS underwent primary fascial closure. In eight of these patients (47%), abdominal and/or pelvic packing for hemostasis was performed. All patients with ACS required decompressive emergency laparotomies because of physiologic derangements. The time between primary laparotomy and decompressive laparotomy was 12.9 ± 2.0 hrs. Emergency decompression of the abdomen resulted in a significant increase in the cardiac index (+146%), tidal volume (+133%), Horowitz quotient (+156%), and urine output (+1557%), whereas bladder pressure (−63%), heart rate (−19%), central venous pressure (−30%), pulmonary artery occlusion pressure (−43%), peak airway pressure (−31%), partial pressure arterial carbon dioxide (−30%), and lactate (−40%) markedly (p < .05) decreased. In two multiply injured patients with additional head trauma, ACS caused a critical increase of the intracranial pressure, which markedly dropped after the release of abdominal tension. Conclusions Risk factors for the occurrence of ACS are severe abdominal and/or pelvic trauma, which require laparotomy and packing for the control of hemorrhage. The ACS occurs within hours and causes life-threatening physiologic derangements and a critical rise in intracranial pressure in patients with combined abdominal/pelvic and head trauma. Decompressive laparotomy immediately restores impaired organ functions. In patients at risk, the continuous measurement of urinary bladder pressure as a simple, noninvasive, and less expensive diagnostic tool for early detection of elevated intra-abdominal pressure is mandatory.

Hydroxyethyl starches: different products--different effects.

With the development of a new generation of hydroxyethyl starches (HES), there has been renewed interest in their clinical potential. High doses of first- and second-generation HES were associated with adverse effects on renal function, coagulation, and tissue storage, thereby limiting their clinical applicability. Newer HES products have lower molar substitution and in vivo molecular weight, resulting in more rapid metabolism and clearance. In this review article, the differences between HES generations are highlighted, with particular emphasis on the improved safety profile of the third generation products. These improvements have been achieved with no loss of efficacy, and they contradict the assumption that efficacy of HES solutions is directly linked to plasma concentration. The impact of source material on structure and pharmacokinetics is highlighted, and the role of the carrier solution is critically assessed.

Intrathecal and serum interleukin-6 and the acute-phase response in patients with severe traumatic brain injuries.

Patients with severe traumatic brain injury (TBI) show a profound acute-phase response. Because interleukin-6 (IL-6) is an important mediator of these pathophysiological changes, IL-6 levels were monitored in the cerebrospinal fluid (CSF) and serum of 20 patients with severe isolated TBI. All patients received indwelling ventricular catheters for intracranial pressure monitoring and for release of CSF when intracranial pressure exceeded 15 mmHg. CSF and blood samples were drawn daily for up to 14 days. The CSF/serum albumin ratio (QA) served as a parameter of blood brain barrier dysfunction. Differential blood counts as well as the acute-phase proteins C-reactive protein, alpha 1-antitrypsin, and fibrinogen were recorded. IL-6 was detected in all CSF samples and reached values of up to 31,000 pg/mL, while serum levels remained significantly lower (alpha < or = .01) and never exceeded 1,100 pg/mL the entire study period. A correlation between CSF and serum IL-6 was found initially after the trauma and corresponded to a severe dysfunction of the blood brain barrier (r = .637, p = .001). Maximum IL-6 concentrations in serum correlated with peak levels of acute-phase proteins (C-reactive protein, alpha 1-antitrypsin, and fibrinogen). With regard to blood cell count, an initial leukocytosis combined with a borderline lymphocytopenia was observed. Thrombocytes decreased to a subnormal level during the first few days, but reached supranormal numbers by the end of the study period. Our results show that the increase of IL-6 levels in CSF and serum is followed by a profound acute-phase response in patients with TBI. Because cytokine concentrations are significantly lower in serum compared with CSF, we hypothesize that IL-6 produced in the central nervous system may play a role in initiating the acute-phase response.

Relationship between procalcitonin plasma levels and severity of injury, sepsis, organ failure, and mortality in injured patients.

Objective: To compare procalcitonin (PCT) plasma levels of injured patients with the incidence and severity of systemic inflammatory response syndrome (SIRS), infection, and multiple organ dysfunction syndrome (MODS) and to assess the predictive value of PCT for these posttraumatic complications. Design: Retrospective study comparing patients with mechanical trauma in terms of severity of injury, development of infectious complications, and organ dysfunctions. Setting: Level I trauma center with emergency room, intensive care unit, and research laboratory. Patients: Four hundred five injured patients with an Injury Severity Score of ≥9 points were enrolled in this study from January 1994 to February 1996. Interventions: Blood samples were collected on the day of admission and on days 1, 3, 5, 7, 10, 14, and 21 thereafter. Measurements and Main Results: We determined PCT serum levels using a specific immunoluminometric assay. We retrospectively evaluated the occurrence of SIRS, sepsis, and MODS using patients’ charts. Mechanical trauma led to increased PCT plasma levels dependent on the severity of injury, with peak values on days 1 and 3 (p < .05) and a continuous decrease within 21 days after trauma. Patients who developed SIRS demonstrated a significant (p < .05) increase of peak PCT plasma levels compared with patients without SIRS. The highest PCT plasma concentrations early after injury were observed in patients with sepsis (6.9 ± 2.5 ng/mL; day 1) or severe MODS (5.7 ± 2.2 ng/mL; day 1) with a sustained increase (p < .05) for 14 days compared with patients with an uneventful posttraumatic course (1.1 ± 0.2 ng/mL). Moreover, these increased PCT plasma levels during the first 3 days after trauma predicted (p < .0001; logistic regression analysis) severe SIRS, sepsis, and MODS. Conclusions: These data indicate that PCT represents a sensitive and predictive indicator of sepsis and severe MODS in injured patients. Routine analysis of PCT levels seems to aid early recognition of these posttraumatic complications. Thus, PCT may represent a useful marker to monitor the inflammatory status of injured patients at risk.

Repetitive Large-Dose Infusion of the Novel Hydroxyethyl Starch 130/0.4 in Patients with Severe Head Injury

In this prospective, controlled, randomized, single-center study, we investigated the safety of repetitive large-dose infusion of a novel hydroxyethyl starch solution (6% HES 130/0.4) in cranio-cerebral trauma patients. Patients were randomized to receive either HES 130/0.4 (n = 16) at repetitive doses of up to 70 mL · kg−1 · d−1 (which is the largest HES dose reported in the literature) or the control HES 200/0.5 (n = 15) up to its approved dose limit of 33 mL · kg−1 · d−1 followed by human albumin up to a total dose (HES 200/0.5 + albumin) of 70 mL · kg−1 · d−1. We found no differences between groups in mortality, renal function, bleeding complications, and use of blood products. There were also no major differences in coagulation variables. However, at some time points, factor VIII, von Willebrand factor, and ristocetin cofactor were higher in the HES 130/0.4 group despite the large HES doses administered. We conclude that HES 130/0.4 can safely be used in critically ill head trauma patients over several days at doses of up to 70 mL · kg−1 · d−1.

Hypocretin-1 (orexin A) deficiency in acute traumatic brain injury

Hypocretin-1 is involved in the regulation of the sleep-wake cycle. The authors prospectively assessed CSF hypocretin-1 levels in 44 consecutive patients with acute traumatic brain injury (TBI). Compared with controls, hypocretin-1 levels were abnormally lower in 95% of patients with moderate to severe TBI and in 97% of patients with posttraumatic brain CT changes. Hypocretin-1 deficiency after TBI may reflect hypothalamic damage and be linked with the frequent development of posttraumatic sleep-wake disorders.

Loss of hypocretin (orexin) neurons with traumatic brain injury

Chronic, daytime sleepiness is a major, disabling symptom for many patients with traumatic brain injury (TBI), but thus far, its etiology is not well understood. Extensive loss of the hypothalamic neurons that produce the wake‐promoting neuropeptide hypocretin (orexin) causes the severe sleepiness of narcolepsy, and partial loss of these cells may contribute to the sleepiness of Parkinson disease and other disorders. We have found that the number of hypocretin neurons is significantly reduced in patients with severe TBI. This observation highlights the often overlooked hypothalamic injury in TBI and provides new insights into the causes of chronic sleepiness in patients with TBI. Ann Neurol 2009;66:555–559

Increased expression of toll-like receptor-2 and -4 on leukocytes from patients with sepsis

The reduced responsiveness of monocytes or granulocytes toward endotoxin (endotoxin tolerance) during sepsis may depend on Toll-like receptors (TLR). The expression of TLR-2 and TLR-4 was measured on neutrophils (PMN) and monocytes from patients with sepsis (n = 21) or healthy controls (n = 12). Leukocytes (1 × 106/mL) were incubated at 37°C with or without a TLR-4 (LPS 1 μg/mL) or a TLR-2 ligand (MALP-2 2 nM). Surface expression of TLR-2 and TLR-4 at 0, 4, and 16 h was determined in FACS after staining with specific antibodies. The release of IL-8 and TNF-α was measured by ELISA. Freshly isolated PMN from patients with sepsis exhibited significantly (P < 0.05) higher mean fluorescence for TLR-2 (78.0 ± 18.6) and TLR-4 (11.4 ± 2.3) than controls (12.8 ± 2.2 and 2.3 ± 0.4). Similarly, monocytes from patients exhibited higher TLR-2 and TLR-4 expression (300.8 ± 40.6 and 92.7 ± 12.1) than cells from controls (149.5 ± 27.1 and 52.2 ± 7.6). In patients with sepsis, expression of TLR-2 and TLR-4 on PMN increased during 16 h of incubation (106.2 ± 22.1 and 34.5 ± 5.3), whereas it remained unchanged in controls (19.3 ± 6.1 and 5.4 ± 1.9). Incubation with LPS or MALP-2 had no effect on TLR-4 or TLR-2 expression in cells from either controls or patients. Despite increased TLR expression in cells from patients with sepsis, the endotoxin-induced release of TNF-α and IL-8 was indistinguishable from that in controls. Therefore, the endotoxin tolerance seen in patients with sepsis does not depend solely on TLR-2 or TLR-4 expression, and other mechanisms must be involved.

Modafinil ameliorates excessive daytime sleepiness after traumatic brain injury.

Background: Excessive daytime sleepiness (EDS) and fatigue are common symptoms after traumatic brain injury (TBI), but there is no specific treatment for affected patients. With this pilot study, we aimed at studying the effect of daily modafinil on posttraumatic EDS and fatigue. Methods: We conducted a prospective, double-blind, randomized, placebo-controlled pilot study in 20 patients with TBI who had fatigue or EDS or both. After baseline examinations (questionnaires including the Epworth Sleepiness Scale to assess EDS and the Fatigue Severity Scale to assess fatigue, actigraphy, polysomnography, maintenance of wakefulness test, and psychomotor vigilance test), 10 patients received 100 to 200 mg modafinil every morning, and 10 patients were treated with placebo. After a 6-week treatment period, all examinations were repeated. Results: EDS improved significantly in patients with TBI who were treated with modafinil, compared with the placebo group. Similarly, the ability to stay awake on the maintenance of wakefulness test improved only in the modafinil group. Modafinil, however, had no impact on posttraumatic fatigue. Clinically relevant side effects were not observed. Conclusion: This study indicates that modafinil is effective and well tolerated in the treatment of posttraumatic EDS but not of fatigue. Classification of evidence: This study provides Class I evidence that modafinil (100–200 mg daily) improves posttraumatic EDS compared with placebo. This study provides Class I evidence that modafinil (100–200 mg daily) does not improve posttraumatic fatigue compared with placebo.

Noninvasive cardiac output and blood pressure monitoring cannot replace an invasive monitoring system in critically ill patients

BackgroundMonitoring of cardiac output and blood pressure are standard procedures in critical care medicine. Traditionally, invasive techniques like pulmonary artery catheter (PAC) and arterial catheters are widely used. Invasiveness bears many risks of deleterious complications. Therefore, a noninvasive reliable cardiac output (CO) and blood pressure monitoring system could improve the safety of cardiac monitoring. The aim of the present study was to compare a noninvasive versus a standard invasive cardiovascular monitoring system.MethodsNexfin HD is a continuous noninvasive blood pressure and cardiac output monitor system and is based on the development of the pulsatile unloading of the finger arterial walls using an inflatable finger cuff. During continuous BP measurement CO is calculated. We included 10 patients with standard invasive cardiac monitoring system (pulmonary artery catheter and arterial catheter) comparing invasively obtained data to the data collected noninvasively using the Nexfin HD.ResultsCorrelation between mean arterial pressure measured with the standard arterial monitoring system and the Nexfin HD was r2 = 0.67 with a bias of -2 mmHg and two standard deviations of ± 16 mmHg. Correlation between CO derived from PAC and the Nexfin HD was r2 = 0.83 with a bias of 0.23 l/min and two standard deviations of ± 2.1 l/min; the percentage error was 29%.ConclusionAlthough the noninvasive CO measurement appears promising, the noninvasive blood pressure assessment is clearly less reliable than the invasively measured blood pressure. Therefore, according to the present data application of the Nexfin HD monitoring system in the ICU cannot be recommended generally. Whether such a tool might be reliable in certain critically ill patients remains to be determined.