Thea Koch

Successful resuscitation of a patient with ropivacaine-induced asystole after axillary plexus block using lipid infusion*

Ropivacaine 1% 40 ml was mistakenly injected as part of an axillary plexus block in an 84‐year‐old woman. After 15 min the patient complained of dizziness and drowsiness and developed a generalised tonic‐clonic seizure followed by an asystolic cardiac arrest. After 10 min of unsuccessful cardiopulmonary resuscitation, a bolus of 100 ml of Intralipid 20% (2 ml.kg−1) was administered followed by a continuous infusion of 10 ml.min−1. After a total dose of 200 ml of Intralipid 20% had been given spontaneous electrical activity and cardiac output was restored. The patient recovered completely. We believe the cardiovascular collapse was secondary to ropivacaine absorption following the accidental overdose. This case shows that lipid infusion may have a beneficial role in cases of local anaesthetic toxicity when conventional resuscitation has been unsuccessful.

Omega-3 fatty acids improve the diagnosis-related clinical outcome.

Objective:Supplementation of clinical nutrition with omega-3 fatty acid in fish oil exerts immune-modulating and organ-protective effects, even after short-term application. The aim of this study was to evaluate dose-dependent effects of parenteral supplementation of a 10% fish oil emulsion (Omegaven, Fresenius-Kabi, Bad Homburg, Germany) on diagnosis- and organ failure–related outcome. Design:Prospective, open label, multiple-center trial. Patients and Methods:A total of 661 patients from 82 German hospitals receiving total parenteral nutrition for ≥3 days were enrolled in this study. The sample included 255 patients after major abdominal surgery, 276 with peritonitis and abdominal sepsis, 16 with nonabdominal sepsis, 59 after multiple trauma, 18 with severe head injury, and 37 with other diagnoses. The primary study end point was survival; secondary end points were length of hospital stay and use of antibiotics with respect to the primary diagnosis and the extent of organ failure. Multiple quasi-linear and logistic regression models were used for calculating diagnosis-related fish oil doses associated with best outcome. Results:The patients enrolled in this survey were (mean ± sd) 62.8 ± 16.5 yrs old, with a body mass index of 25.1 ± 4.2 and Simplified Acute Physiology Score (SAPS) II score of 32.2 ± 13.6. Length of hospital stay was 29.1 ± 18.7 days (12.5 ± 14.8 days in the intensive care unit). Total parenteral nutrition, including fish oil (mean, 0.11 g·kg−1·day−1), was administered for 8.7 ± 7.5 days and lowered hospital mortality as predicted by Simplified Acute Physiology Score II from 18.9% (95% confidence interval, 17.4–20.4%) to 12.0% (p < .001). The fish oil dose·kg−1·day−1 did correlate with beneficial outcome (intensive care unit stay, hospital stay, mortality). Fish oil had the most favorable effects on survival, infection rates, and length of stay when administered in doses between 0.1 and 0.2 g·kg−1·day−1. Lower antibiotic demand by 26% was observed when doses of 0.15–0.2 g·kg−1·day−1 were infused as compared with doses of <0.05 g·kg−1·day−1. After peritonitis and abdominal sepsis, multiple quasi-linear regression models revealed a fish oil dose for minimizing intensive care unit stay of 0.23 g·kg−1·day−1 and an inverse linear relationship between dosage and intensive care unit stay in major abdominal surgery. Conclusion:Administration of omega-3 fatty acid may reduce mortality, antibiotic use, and length of hospital stay in different diseases. Effects and effect sizes related to fish oil doses are diagnosis dependent. In view of the lack of substantial study literature concerning diagnosis-related nutritional single-substrate intervention in the critically ill, the present data can be used in formulating hypotheses and may serve as reference doses for randomized, controlled studies, which may, for instance, confirm the value of omega-3 fatty acid in the adjunctive therapy of peritonitis and abdominal sepsis.

Lipid Mediators in Inflammatory Disorders

SummaryDuring the past few decades, intensive collaborative research in the fields of chronic and acute inflammatory disorders has resulted in a better understanding of the pathophysiology and diagnosis of these diseases. Modern therapeutic approaches are still not satisfactory and shock, sepsis and multiple organ failure remain the great challenge in intensive care medicine. However, the treatment of inflammatory diseases like rheumatoid arthritis, ulcerative colitis or psoriasis also represents an unresolved problem.Many factors contribute to the complex course of inflammatory reactions. Microbiological, immunological and toxic agents can initiate the inflammatory response by activating a variety of humoral and cellular mediators. In the early phase of inflammation, excessive amounts of interleukins and lipid-mediators are released and play a crucial role in the pathogenesis of organ dysfunction. Arachidonic acid (AA), the mother substance of the pro-inflammatory eicosanoids, is released from membrane phospholipids in the course of inflammatory activation and is metabolised to prostaglandins and leukotrienes.Various strategies have been evaluated to control the excessive production of lipid mediators on different levels of biochemical pathways, such as inhibition of phospholipase A2, the trigger enzyme for release of AA, blockade of cyclooxygenase and lipoxygenase pathways and the development of receptor antagonists against platelet activating factor and leukotrienes. Some of these agents exert protective effects in different inflammatory disorders such as septic organ failure, rheumatoid arthritis or asthma, whereas others fail to do so. Encouraging results have been obtained by dietary supplementation with long chain ω-3 fatty acids like eicosapentaenoic acid (EPA). In states of inflammation, EPA is released to compete with AA for enzymatic metabolism inducing the production of less inflammatory and chemotactic derivatives.

Omega-3 fatty acids improve liver and pancreas function in postoperative cancer patients.

Epidemiologic studies have indicated that high intake of saturated fat and/or animal fat increases the risk of colon and breast cancer. Omega‐3 PUFAs in fish oil (FO) can inhibit the growth of human cancer cells in vitro and in vivo. These effects are related to the uptake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into the cellular substrate pool and their competitive metabolism with arachidonic acid (AA) at the cyclooxygenase and 5‐lipoxygenase levels. The metabolites of EPA and DHA have less inflammatory and immunosuppressant potency than the substances derived from AA. Based on previous experimental data, we hypothesized that FO supplementation after major abdominal cancer surgery would improve hepatic and pancreatic function. Ours was a prospective, randomized, double‐blinded clinical trial on 44 patients undergoing elective major abdominal surgery, randomly assigned to receive total parenteral nutrition (TPN) supplemented with either soybean oil (SO 1.0 g/kg body weight daily, n = 20) for 5 days or a combination of FO and SO (FO 0.2 + SO 0.8 g/kg body weight daily, n = 24). Compared to pure SO supplementation in the postoperative period, FO significantly reduced ASAT [0.8 ± 0.1 vs. 0.5 ± 0.1 mmol/(l · sec)], ALAT [0.9 ± 0.1 vs. 0.6 ± 0.1 mmol/(l · sec)], bilirubin (16.1 ± 5.3 vs. 6.9 ± 0.6 mmol/l), LDH (7.7 ± 0.4 vs. 6.7 ± 0.4 mmol/(l · sec) and lipase (0.6 ± 0.1 vs. 0.4 ± 0.1 μmol/(l · sec) in the postoperative course. Moreover, patients with increased risk of sepsis (IL‐6/IL‐10 ratio >8) showed a tendency to shorter ICU stay (18 hr) under omega‐3 PUFA treatment. Weight loss as encountered after the SO emulsion of 1.1 ± 2.2 kg was absent in the FO group. After major abdominal tumor surgery, FO supplementation improved liver and pancreas function, which might have contributed to the faster recovery of patients.

The Effects of Lipid Infusion on Myocardial Function and Bioenergetics in L-Bupivacaine Toxicity in the Isolated Rat Heart

BACKGROUND:It is unclear whether improved metabolism or a “lipid sink” effect of lipid infusion is responsible for the positive effects in local anesthetic-induced myocardial depression. METHODS:We used an isolated rat heart, constant-pressure perfused, nonrecirculating Langendorff preparation and exposed hearts to 5 &mgr;g/mL l-bupivacaine and 9 &mgr;L/mL lipid emulsion. Hearts were freeze-clamped and energy was charge measured by HPLC. In a second experiment the effects of pacing hearts was evaluated. The effects of lipid addition on local anesthetic concentrations in Krebs–Henseleit buffer and human plasma were examined by using a mass spectrometer. RESULTS:With spontaneously beating hearts l-bupivacaine led to a significant decrease in heart rate (to 74% ± 7% of baseline), +dP/dt (69% ± 7%), systolic pressure (78% ± 6%), coronary flow (61% ± 8%), and to an increase in PR (177% ± 52%) and QRS intervals (166% ± 36%). Lipid infusion exerted a positive inotropic effect, significantly augmenting +dP/dt and systolic pressure back to 94% ± 11% and 102% ± 16% of baseline in l-bupivacaine-treated hearts. Heart rate, coronary flow, PR, and QRS intervals remained unchanged after lipid intervention. Lipid infusion in paced hearts had a significant effect on +dP/dt, systolic pressure, and Mvo2. Neither l-bupivacaine nor lipids had an effect on energy charge. A lipid concentration of 500 &mgr;L/mL plasma was necessary to effect changes in the plasma concentration of local anesthetics. CONCLUSION:Lipid application in l-bupivacaine-induced cardiac depression had a significant positive inotropic effect, which we would attribute to a direct inotropic effect. However, in an isolated heart model, indirect, local anesthetic plasma-binding effect of lipids cannot be excluded.

Variable Tidal Volumes Improve Lung Protective Ventilation Strategies in Experimental Lung Injury

RATIONALE Noisy ventilation with variable Vt may improve respiratory function in acute lung injury. OBJECTIVES To determine the impact of noisy ventilation on respiratory function and its biological effects on lung parenchyma compared with conventional protective mechanical ventilation strategies. METHODS In a porcine surfactant depletion model of lung injury, we randomly combined noisy ventilation with the ARDS Network protocol or the open lung approach (n = 9 per group). MEASUREMENTS AND MAIN RESULTS Respiratory mechanics, gas exchange, and distribution of pulmonary blood flow were measured at intervals over a 6-hour period. Postmortem, lung tissue was analyzed to determine histological damage, mechanical stress, and inflammation. We found that, at comparable minute ventilation, noisy ventilation (1) improved arterial oxygenation and reduced mean inspiratory peak airway pressure and elastance of the respiratory system compared with the ARDS Network protocol and the open lung approach, (2) redistributed pulmonary blood flow to caudal zones compared with the ARDS Network protocol and to peripheral ones compared with the open lung approach, (3) reduced histological damage in comparison to both protective ventilation strategies, and (4) did not increase lung inflammation or mechanical stress. CONCLUSIONS Noisy ventilation with variable Vt and fixed respiratory frequency improves respiratory function and reduces histological damage compared with standard protective ventilation strategies.

One-lung Ventilation with High Tidal Volumes and Zero Positive End-expiratory Pressure Is Injurious in the Isolated Rabbit Lung Model

We tested the hypothesis that one-lung ventilation (OLV) with high tidal volumes (Vt) and zero positive end-expiratory pressure (PEEP) may lead to ventilator-induced lung injury. In an isolated, perfused rabbit lung model, Vt and PEEP were set to avoid lung collapse and overdistension in both lungs, resulting in a straight pressure-time (P-vs-t) curve during constant flow. Animals were randomized to (a) nonprotective OLV (left lung) (n = 6), with Vt values as high as before randomization and zero PEEP; (b) protective OLV (left lung) (n = 6), with 50% reduction of Vt and maintenance of PEEP as before randomization; and (c) control group (n = 6), with ventilation of two lungs as before randomization. The nonprotective OLV was associated with significantly smaller degrees of collapse and overdistension in the ventilated lung (P < 0.001). Peak inspiratory pressure values were higher in the nonprotective OLV group (P < 0.001) and increased progressively throughout the observation period (P < 0.01). The mean pulmonary artery pressure and lung weight gain values, as well as the concentration of thromboxane B2, were comparatively higher in the nonprotective OLV group (P < 0.05). A ventilatory strategy with Vt values as high as those used in the clinical setting and zero PEEP leads to ventilator-induced lung injury in this model of OLV, but this can be minimized with Vt and PEEP values set to avoid lung overdistension and collapse.

Noisy pressure support ventilation: A pilot study on a new assisted ventilation mode in experimental lung injury*

Objective:To describe and evaluate the effects of the new noisy pressure support ventilation (noisy PSV) on lung physiologic variables. Design:Crossover design with four modes of mechanical ventilation. Setting:Experimental research facility of a university hospital. Subjects:A total of 12 pigs weighing 25.0–36.5 kg. Interventions:Animals were anesthetized, the trachea was intubated, and lungs were ventilated with a mechanical ventilator (volume-controlled mode). Acute lung injury was then induced by surfactant depletion. Biphasic intermittent airway pressure/airway pressure release ventilation (BIPAP/APRV) was initiated, and anesthesia depth was decreased to allow spontaneous breathing. After that, each animal was ventilated with four different modes of assisted mechanical ventilation (1 hr each, Latin squares sequence): 1) PSV, 2) PSV combined with intermittent sighs (PSV + Sighs), 3) BIPAP/APRV + spontaneous breathing, and 4) noisy PSV with random variation of pressure support (normal distribution). The mean level of pressure support was set identical in all PSV forms. Measurements and Main Results:We found that noisy PSV increased tidal volume variability compared with PSV and PSV + Sighs (19% vs. 5% and 7%, respectively, p < .05) independently from the inspiratory effort; improved oxygenation and reduced venous admixture but did not affect the amount of nonaerated lung tissue as compared with other assisted ventilation modes; reduced mean airway pressure at comparable minute ventilation; redistributed pulmonary blood flow toward nondependent lung regions similar to other PSV forms, whereas BIPAP/APRV + spontaneous breathing did not; and reduced the inspiratory effort and cardiac output in comparison with BIPAP/APRV + spontaneous breathing. Conclusions:In the surfactant depletion model of acute lung injury, the new noisy PSV increased the variability of the respiratory pattern and improved oxygenation by a redistribution of perfusion toward the ventilated nondependent lung regions with simultaneous lower mean airway pressure, comparable minute ventilation, and no increase in the inspiratory effort or cardiac output.

Excellence in performance and stress reduction during two different full scale simulator training courses: A pilot study☆☆☆

BACKGROUND Simulator training is well established to improve technical and non-technical skills in critical situations. Few data exist about stress experienced during simulator training. This study aims to evaluate performance and stress in intensivists before and after two different simulator-based training approaches. METHODS Thirty-two intensivists took part in one of six 1-day simulator courses. The courses were randomised to either crew resource management (CRM) training, which contains psychological teaching and simulator scenarios, or classic simulator training (MED). Before and after the course each participant took part in a 10-min test scenario. Before (T1) and after (T2) the scenario, and then again 15 min later (T3), saliva samples were taken, and amylase and cortisol were measured. Non-technical skills were evaluated using the Anaesthetists Non-Technical Skills (ANTS) assessment tool. Clinical performance of the participants in the test scenarios was rated using a checklist. RESULTS Twenty-nine participants completed the course (17-CRM, 12-MED). ANTS scores as well as clinical performances were significantly better in the post-intervention scenario, with no differences between the groups. Both cortisol concentration and amylase activity showed a significant increase during the test scenarios. In the post-intervention scenario, the increase in amylase but not cortisol was significantly smaller. There were no differences between the CRM and MED group. CONCLUSIONS High fidelity patient simulation produces significant stress. After a 1-day simulator training, stress response measured by salivary alpha-amylase was reduced. Clinical performance and non-technical skills improved after 1 day of simulator training. Neither stress nor performance differed between the groups.

N-acetylcysteine reduces respiratory burst but augments neutrophil phagocytosis in intensive care unit patients.

ObjectiveThe antioxidant N-acetylcysteine (NAC) has been shown to attenuate septic tissue injury. To evaluate whether NAC affects host defense mechanisms in critically ill patients, thus predisposing to increased risk of infection, the current study focuses on neutrophil phagocytotic and burst activity after treatment with NAC. DesignProspective, randomized, clinical trial. SettingTwelve-bed operative intensive care unit in a university hospital. PatientsThirty patients diagnosed with sepsis/systemic inflammatory response syndrome, or multiple trauma. InterventionsPatients were randomly assigned to receive either NAC (n = 15) for 4 days in increasing dosages (day 1: 6 g; day 2: 12 g; days 3 and 4: 18 g) or a mucolytic basis dosage of NAC (3 × 300 mg/day [control]; n = 15), respectively. Measurements and Main Results Blood samples were taken before NAC high-dose infusion (day 1), after increasing doses of NAC (days 3 and 5) and 4 days after the last high-dose treatment (day 8). Neutrophil oxidative burst activity after stimulation with Escherichia coli and polymorphonuclear phagocytosis were determined in a flow cytometric assay. Baseline values of polymorphonuclear functions were comparable in both groups. NAC high-dose treatment resulted in a significantly improved phagocytosis activity compared with control patients. In contrast to this, polymorphonuclear burst activity was significantly reduced in the NAC high-dose treated group on day 3. ConclusionThese findings suggest that infusion of NAC in high doses affects granulocyte functions in critically ill patients. Antimicrobial host defense requires the effective sequence of cell adhesion, phagocytosis, and bactericidal respiratory burst. The enhanced phagocytotic activity might be a compensatory mechanism in states of impaired respiratory burst to maintain tissue sterility. For certain mechanisms of disease, the effects observed might be favorable (e.g., ischemia/reperfusion, endothelial cell activation), for others (infection) this might be detrimental.