Christian von Heymann

Validity and reliability of the DDS for severity of delirium in the ICU.

Introduction: Until now, there has been no gold standard for monitoring delirium in intensive care unit (ICU) patients. In this prospective cohort study, a new score, the Delirium Detection Score (DDS), for severity of delirium in the ICU was evaluated.Methods: After ethical approval and written informed consent, intensive care doctors and nurses assessed 1073 consecutive patients in surgical ICUs using the DDS together with the Ramsay Sedation Scale (RSS). The DDS is composed of eight criteria (orientation, hallucination, agitation, anxiety, seizures, tremor, paroxysmal sweating, and altered sleepwake rhythm). Additionally, intensive care doctors had to document the Sedation-Agitation Scale (SAS) combined with a defined clinical assessment. For interrater reliability, pair of evaluators assessed patients in a blinded fashion at the same time.Results: RSS1 (9%) was associated with a significantly (p<0.001) higher DDS than RSS levels 2–6. The DDS increased with the severity of delirium (p< 0.001). The receiver operating characteristics (ROC) for the differentiation between no delirium (SAS<4) and symptoms of delirium at all (SAS 5–7) showed an area under the curve (AUC) of 0.802 (95% confidential interval (CI): 0.719–0.898; p<0.001) and 69% sensitivity and 75% specificity was determined. For reliability, a Cronbach’s α of 0.667 was calculated. The paired comparisons revealed an intraclass correlation between 0.642 and 0.758.Conclusion: The DDS demonstrated good validity with excellent sensitivity and specificity for delirium. The severity of delirium can be more accurately estimated by the DDS. By its composition of several items, the DDS might help to start a symptom-guided therapy immediately.

Preoperative oral carbohydrate administration to ASA III-IV patients undergoing elective cardiac surgery

In this study we investigated the effects of preoperative oral carbohydrate administration on postoperative insulin resistance (PIR), gastric fluid volume, preoperative discomfort, and variables of organ dysfunction in ASA physical status III-IV patients undergoing elective cardiac surgery, including those with noninsulin-dependent Type-2 diabetes mellitus. Before surgery, 188 patients were randomized to receive a clear 12.5% carbohydrate drink (CHO), flavored water (placebo), or to fast overnight (control). CHO and placebo were treated in double-blind format and received 800 mL of the corresponding beverage in the evening and 400 mL 2 h before surgery. Patients were monitored from induction of general anesthesia until 24 h postoperatively. Exogenous insulin requirements to control blood glucose levels ≤10.0 mmol/L were used as a marker for PIR. Gastric fluid volume was measured by passive gastric reflux and preoperative discomfort using visual analog scales. Postoperative clinical and surgical data were recorded. Blood glucose levels and insulin requirements did not differ between groups. Patients receiving CHO and placebo were less thirsty compared with controls (P < 0.01 and P = 0.06, respectively). Ingested liquids did not cause increased gastric fluid volume or other adverse events. The CHO group required less intraoperative inotropic support after initiation of cardiopulmonary bypass weaning (P < 0.05). In conclusion, preoperative CHO administration before cardiac surgery does not affect PIR. Clear fluids reduce thirst and may be recommended as a safe procedure in ASA III-IV patients. Further research is indicated to investigate possible cardioprotective effects of preoperative CHO intake.

Intermittent high permeability hemofiltration in septic patients with acute renal failure

ObjectiveHigh permeability hemofiltration (HP-HF) is a new renal replacement modality designed to facilitate the elimination of cytokines in sepsis. Clinical safety data on this new procedure is still lacking. This study investigates the effects of HP-HF on the protein and coagulation status as well as on cardiovascular hemodynamics in patients with septic shock. In addition, the clearance capacity for interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) is analyzed.DesignProspective, single-center pilot trial.SettingUniversity hospital.PatientsSixteen patients with multiple organ failure (MOF) induced by septic shock were studied.InterventionPatients were treated by intermittent high permeability hemofiltration (iHP-HF; nominal cut-off point: 60xa0kilodaltons). Intermittent HP-HF was performed over 5xa0days for 12xa0h per day and alternated with conventional hemofiltration.Measurements and resultsIntermittent HP-HF proved to be a safe hemofiltration modality in regard to cardiovascular hemodynamics and its impact on the coagulation status. However, transmembrane protein loss occurred and cumulative 12-h protein loss was 7.60xa0g (IQR: 6.2–12.0). The filtration capacity for IL-6 was exceptionally high. The IL-6 sieving coefficient approximated 1 throughout the study period. The total plasma IL-6 burden, estimated by area under curve analysis, declined over time (p<0.001 vs baseline). The TNF-α elimination capacity was poor.ConclusionsHigh permeability hemofiltration is a new approach in the adjuvant therapy of sepsis that facilitates the elimination of cytokines. HP-HF alternating with conventional hemofiltration is well tolerated. Further studies are needed to analyze whether HP-HF is able to mitigate the course of sepsis.

Increased Interleukin-6 After Cardiac Surgery Predicts Infection

Early diagnosis and treatment of infection after cardiac surgery with cardiopulmonary bypass (CPB) improves outcome. Conventional laboratory tests, such as C-reactive protein and white blood cell count can not distinguish patients with early infection from those with systemic inflammatory response syndrome but without infection. After CPB, there is a systemic release of proinflammatory and antiinflammatory cytokines, including tumor necrosis factor-&agr;, interleukin (IL)-6, and IL-10. We investigated the predictive ability of these variables for infection after cardiac surgery. Forty-six patients with impaired left ventricular ejection fraction (<60%), scheduled for cardiac surgery, were included. Plasma samples were drawn 1 day before and immediately before surgery, on admission to the intensive care unit, and on days 1, 3, and 7 after surgery. Infection was identified according to the criteria of the Centers for Disease Control and Prevention. After surgery 13 patients developed an infection. In patients with infection, confirmed a median of 4 days after surgery, all measurements of IL-6, and IL-10 on postoperative day 3 were significantly increased. Tumor necrosis factor-&agr;, leukocytes, and C-reactive protein were not increased in these patients. Immediately after surgery blood glucose was significantly increased in patients with infection. Increased IL-6 after CPB is predictive of infection after cardiac surgery in patients with impaired left ventricular function.

Activity of clotting factors in fresh-frozen plasma during storage at 4°C over 6 days

BACKGROUND: Fresh‐frozen plasma (FFP) requires thawing, which delays availability. We investigated clotting factor activity and bacterial contamination of FFP when stored at 4°Cu2003±u20032°C for 6u2003days.

Posttraumatic immune modulation in chronic alcoholics is associated with multiple organ dysfunction syndrome.

BACKGROUNDnPatients with chronic alcohol abuse constitute approximately 50% of trauma care patients, and these patients have a two- to fourfold increase in posttraumatic infectious complications. Cytokines such as interleukin-6 (IL-6) and interleukin-10 (IL-10) and the adhesion molecule soluble endothelial selectin (sE-selectin) have been found to play an important role in the initial inflammatory response to trauma and the development of early and late multiple organ dysfunction syndrome (MODS). The aim of this study was to compare the immune modulation and clinical relevance between chronic alcoholic and nonalcoholic patients following trauma.nnnMETHODSnSixty-three patients (37 alcohol abusers, 26 nonalcoholics) were included in this prospective controlled study. IL-6, IL-10, and sE-selectin were determined on admission and on days 2, 4, and 7 following admission to the ICU.nnnRESULTSnOn admission to the ICU but not on the following days of the study period, plasma IL-6, IL-10, and sE-selectin were significantly elevated in chronic alcoholic patients compared with nonalcoholics. The incidence of MODS was significantly higher in chronic alcoholic patients (89% vs. 50%, p < 0.01), whereas the incidence of pneumonia (35% vs. 19%, p < 0.17) and sepsis (14% vs. 0%, p < 0.07) did not reach statistical significance.nnnCONCLUSIONnThe significantly elevated levels of IL-6, IL-10, and sE-selectin in chronic alcoholic trauma patients on admission to the ICU could play an important role in the development of MODS in intensive care. In patients with high levels of inflammatory mediators, immune modulatory treatment before the development of MODS may be considered.

Clonidine attenuated early proinflammatory response in T-cell subsets after cardiac surgery

T-cells play a central role in the immune response to injury. Cardiac surgery is associated with significant risk of systemic inflammatory response syndrome and subsequent unbalanced induction of proinflammatory cytokines. As clonidine has immunomodulating properties via reducing sympathetic activity, this study involved the analysis of T-cell function in the early postoperative period in patients undergoing coronary artery bypass graft surgery. Forty patients undergoing cardiac surgery were randomly allocated to one of the following groups: clonidine group (n = 20) [clonidine 1 &mgr;g kg−1 h−1] and placebo group (n = 20). Study medication was started after induction of anesthesia and maintained until 6 h after surgery. Blood samples to determine Th1 and Th2 cells and cytotoxic lymphocytes (Tc1 and Tc2 cells) were drawn preoperatively, on admission to the intensive care unit, 6 and 12 h postoperatively as well as on the morning of days 1 and 2 after surgery. In the clonidine group significantly lower levels of Th1/Th2 ratios as well as Tc1/Tc2 ratios were found 6 h postoperatively compared to the placebo group (P < 0.05). Clonidine changed the ratio of T-lymphocyte subpopulations in peripheral blood in favor of a proinflammatory response, which might be favorable for maintaining immune balance after surgery.

Thawing procedures and the time course of clotting factor activity in fresh-frozen plasma: a controlled laboratory investigation.

BACKGROUND:In this study, we evaluated the effects of the thawing process of 2 commercially available devices on the activity of clotting factors, inhibitors and activation markers of the hemostatic system in fresh-frozen plasma (FFP). In an experimental procedure, FFP was thawed under running warm water at 42°C. METHODS:Plasma of 20 healthy donors was sampled, separated, and distributed in 3 plasma bags. Within 2 h after sampling plasma bags was frozen at a temperature of −30°C to −40°C and stored for at least 8 wk. After sampling (baseline) as well as immediately and 1, 2, 4, and 6 h after thawing, the activity of FV, FVII, FVIII, fibrinogen, fibrin monomers (FM), d-dimers (DD), α2-antiplasmin (α2-AP), and protein S (PS) was determined from each plasma bag. RESULTS:From 1 h to 6 h after thawing, no significant differences in the activity of the investigated coagulation markers dependent on the thawing procedure were found. However, immediately after thawing and independent of the thawing procedure, the activity of FVII was significantly decreased (P < 0.01), whereas FM were significantly increased (P = 0.001). CONCLUSION:The thawing procedures studied exhibited no significant influence on activity and stability of the investigated markers of coagulation over the study period. The decreased activity of FVII and the clinical significance of the increase in FM require further research.

Successful coronary artery bypass graft surgery in severe congenital factor VII deficiency: Perioperative treatment with factor VII concentrate

Successful coronary artery bypass graft surgery in severe congenital factor VII deficiency: Perioperative treatment with factor VII concentrate -

Management of direct oral anticoagulants-associated bleeding in the trauma patient.

Purpose of review This article emphasizes the differentiated management of direct oral anticoagulants (DOACs)-associated bleeding in trauma patients to generate a severity adjusted treatment protocol. Recent findings The management of DOAC-associated bleeding should take severity, mortality risk, and haemodynamic effects of the trauma-induced bleeding into account. Summary The different pharmacological properties of DOACs are important for the management of trauma-induced bleeding. Comorbidities like renal impairment and liver dysfunction prolong their half-life. Patients with minor bleeding in stable clinical condition can be managed by a ‘wait and see’ approach. Moderate bleeding is suggested to be managed by a primarily conservative approach. In life-threatening bleeding, the administration of activated or nonactivated factor concentrates seems justified, together with supportive measures as part of an advanced management protocol. The administration of specific antidotes may be an alternative in the future. A monoclonal antibody to dabigatran (idarucizumab) has recently been approved by the Food and Drug Administration, whereas antidotes to Factor X activated inhibitors (andexanet and aripazine) are still under development. Sufficiently powered studies with clinical and safety outcome measures are still missing for all specific antidotes at this time.