Best practice for perioperative management of patients with cytoreductive surgery and HIPEC.

Due to the significantly improved outcome and quality of life of patients with different tumor entities after cytoreductive surgery (CRS) and HIPEC, there is an increasing number of centers performing CRS and HIPEC procedures. As this procedure is technically challenging with potential high morbidity and mortality, respectively, institutional experience also in the anesthetic and intensive care departments is essential for optimal treatment and prevention of adverse events. Clinical pathways have to be developed to achieve also good results in more comorbid patients with border line indications and extensive surgical procedures. The anesthesiologist has deal with relevant fluid, blood and protein losses, increased intraabdominal pressure, systemic hypo-/hyperthermia, and increased metabolic rate in patients undergoing cytoreductive surgery with HIPEC. It is of utmost importance to maintain or restore an adequate volume by aggressive substitution of intravenous fluids, which counteracts the increased fluid loss and venous capacitance during this procedure. Supplementary thoracic epidural analgesia, non-invasive ventilation, and physiotherapy are recommended to guarantee adequate pain therapy and postoperative extubation as well as fast-track concepts. Advanced hemodynamic monitoring is essential to help the anesthesiologist picking up information about the real-time fluid status of the patient. Preoperative preconditioning is mandatory in patients scheduled for HIPEC surgery and will result in improved outcome. Postoperatively, volume status optimization, early nutritional support, sufficient anticoagulation, and point of care coagulation management are essential. This is an extensive update on all relevant topics for anesthetists and intensivists dealing with CRS and HIPEC.

[Key Points of Intraoperative Diagnostic Measures Performed by Anaesthesiologists]. / Relevante Eckpunkte der intraoperativen anästhesiologischen Diagnostik.

The main focus of surgeons and anaesthesiologists during a surgical procedure is on safety and optimal treatment of the patient. Within the scope of interdisciplinary collaboration, the intraoperative communication between surgeons and anaesthesiologists is the basis of case-, findings- and surgery-phases-adapted patient management. The perioperative monitoring of patients and the implementation of diagnostic measures by anaesthesiologists are essential for optimal patient management. The results of the examinations may significantly determine the course of surgery. Therefore, it is important for surgeons to be familiar with the relevant intraoperative diagnostic measures.

Inter-hospital transfer of ECMO-assisted patients with a portable miniaturized ECMO device: 4 years of experience.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) in patients with severe pulmonary failure is able to keep patients alive until organ regeneration, until shunting out for further diagnostic and therapeutic options or until transportation to specialized centers. Nonetheless, extracorporeal techniques require a high degree of expertise, so that a confinement to specialized centers is meaningful. Following from this requirement, the need for inter-hospital transfer of patients with severely compromised pulmonary function is rising. METHODS: We report about our experience with a portable ECMO system during inter-hospital air or ground transfer of patients with cardiopulmonary failure. RESULTS: The portable ECMO system was used for transportation to the center and in-hospital treatment in 36 patients with an average age of 53 years suffering from respiratory failure. Accordingly, the ECMO system was implanted as a veno-venous extracorporeal system. Pre-ECMO ventilation time was 5.2 (2-9) days. Twelve patients were transported to our institution by ground and 24 patients by air ambulance over a median distance of 46 km. With the assistance of the ECMO device, prompt stabilization of cardiopulmonary function could be achieved in all patients without any technical complications. Post-ECMO ventilation was 9.8 days. Weaning from the ECMO system was successful in 61% of all patients after a median device working period of 12.7 days; median ICU stay was 34 days and a survival rate of 64% of patients was achieved. Technical (8%) and device-associated bleeding (11%)/thromboembolic (8%) complication rates showed very acceptable levels. CONCLUSION: Our experience demonstrates that miniaturized, portable ECMO therapy allows location-independent, out-of-center stabilization of pulmonary compromised patients with consecutive inter-hospital transfer and further in-house treatment, so that sophisticated ECMO therapy can be offered to every patient, even in hospitals with primary healthcare.

First experiences with a combined usage of veno-arterial and veno-venous ECMO in therapy-refractory cardiogenic shock patients with cerebral hypoxemia.

The use of extracorporeal membrane oxygenation (ECMO) is becoming a popular tool in the treatment of cardiogenic shock. We present two case reports where classical veno-arterial peripherally cannulated ECMO therapy proved insufficient with profuse cerebral hypoxemia. After augmenting the setting into veno-veno-arterial ECMO, we achieved a remarkable improvement of all oxygenation parameters. The simultaneous use of veno-venous and veno-arterial ECMO might display as a novel strategy to counteract the coronary and cerebral hypoxemia in veno-arterial ECMO therapy in patients with therapy-refractory cardiogenic shock or in combined cardiopulmonary failure. In this manuscript, the veno-veno-arterial ECMO setup is described in full detail and different venous cannulas are discussed.

Thromboelastometric detection of clotting Factor XIII deficiency in cardiac surgery patients.

AIM(S): In this article, we aimed to investigate plasma Factor XIII levels after extracorporeal circulation in cardiac surgery by thromboelastometric detection, as extracorporeal circulation causes various coagulation disorders due to the exposure of blood to artificial surfaces, inflammatory induction and mechanical destruction of platelets and coagulation factors, which may particularly affect factors with long half-lives, such as Factor XIII. BACKGROUND: Since transfusion algorithms are often empirical and laboratory analysis of Factor XIII plasma levels may not be available 24 h a day, bed-side testing using rotational thromboelastometry (ROTEM) could offer a splendid option to define the cause of excessive peri-operative bleeding disorders in general and Factor XIII levels in particular in a timely manner and thus facilitating exact substitution therapy. METHODS: In this trial, we investigated 25 cardiac surgery patients with extracorporeal bypass times over 100 min. Standard laboratory and ROTEM analyses were performed post-operatively at the time of intensive care unit admission and 6 h later. We implemented EXTEM with additional Factor XIII (teenTEM) as additional test by adding 0·625 IU Factor XIII to standard EXTEM reagents. RESULTS: In this observational study, we could not demonstrate a correlation between Factor XIII and MCFEXTEM , CFTEXTEM or MLEXTEM . Neither Factor XIII plasma levels nor MCFEXTEM could predict blood loss. In accordance with previous findings, we were able to demonstrate increased maximum clot firmness (MCF), decreased clot formation time and decreased maximum lysis by adding Factor XIII in vitro (teenTEM vs EXTEM) indicating an improvement in the coagulation process. As shown before, we also found a strong correlation between MCF and platelet and fibrinogen plasma levels. CONCLUSION: In summary, 'teenTEM' test does not seem to detect Factor XIII deficient patients in cardiac surgery. Furthermore, post-operative blood loss could not be predicted neither by ROTEM nor by laboratory analysis of Factor XIII. In vitro administration of Factor XIII appears to improve laboratory measures of haemostasis.

Immediate effects of individualized heparin and protamine management on hemostatic activation and platelet function in adult patients undergoing cardiac surgery with tranexamic acid antifibrinolytic therapy.

OBJECTIVE: This randomized prospective study was initiated to clarify whether individualized heparin and protamine dosing has immediate effects on hemostatic activation and platelet function in adult cardiac surgery. METHODS: Sixty adults undergoing elective coronary artery bypass grafting (CABG) were assigned to receive individualized heparin and protamine (HMS group, n= 29) or a standard dose (ACT group, n=24). Measures of thrombin generation and Multiplate (Verum Diagnostica, Munich, Germany) platelet function tests were performed before and after cardiopulmonary bypass (CPB). RESULTS: HMS patients received higher heparin (p = 0.006) and lower protamine (p<0.001) doses. Post-CPB, HMS managed patients showed significantly lower thrombin generation (thrombin-antithrombin (TAT) p<0.02) than the ACT group. Moreover, HMS managed patients had a better preservation of platelet function (COL p = 0.013; ADP p = 0.04; TRAP p = 0.04). CONCLUSION: An individualized and stable heparin concentration and appropriate dosing of protamine can reduce thrombin generation and preserve platelet function, even in short-time CPB.

Glutamine and alanine-induced differential expression of intracellular IL-6, IL-8, and TNF-α in LPS-stimulated monocytes in human whole-blood.

To investigate the effects of the commonly-used immunomodulators l-glutamine, l-alanine, and the combination of both l-alanyl-l-glutamine (Dipeptamin(®)) on intracellular expression of IL-6, IL-8, and TNF-α during endotoxemia, lipopolysaccharide (LPS)-stimulated human monocytes in a whole blood system were investigated by flow cytometry. Whole blood of twenty-seven healthy volunteers was stimulated with LPS and incubated with three different amino acid solutions (1. l-glutamine, 2. l-alanine, 3. l-alanyl-l-glutamine, each concentration 2 mM, 5 mM, incubation time 3 h). CD14(+) monocytes were phenotyped in whole-blood and intracellular expression of cytokines was assessed by flow cytometry. Our investigations showed for the first time in whole blood probes, imitating best physiologically present cellular interactions, that l-glutamine caused a dose-independent inhibitory effect on IL-6 and TNF-α production in human monocytes stimulated with LPS. However, l-alanine had contrary effects on IL-6 expression, significantly upregulating expression of IL-6 in LPS-treated monocytes. The impact of l-alanine on the expression of TNF-α was comparable with glutamine. Neither amino acid was able to affect IL-8 production in LPS-stimulated monocytes. The combination of both did not influence significantly IL-6 and IL-8 expression in monocytes during endotoxemia, however strongly reduced TNF-α production. For the regulation of TNF-α, l-glutamine, l-alanine and the combination of both show a congruent and exponentiated downregulating effect during endotoxemia, for the modulation of IL-6, l-glutamine and l-alanine featured opposite regulation leading to a canceling impact of each other when recombining both amino acids.

NF-κB-mediated inverse regulation of fractalkine and CX3CR1 during CLP-induced sepsis.

Fractalkine is a unique member of the CX3C chemokine family by unfolding its potential through the chemokine (C-X3-C motif) receptor 1 (CX3CR1) with dual function acting both as an adhesion molecule and a soluble chemokine. The regulation of this chemokine is still not clear. Therefore, we were interested in the regulation of fractalkine and of CX3CR1 in experimental sepsis. In addition, we investigated the role of NF-κB for the regulation of fractalkine and of CX3CR1. Using a mouse model of cecal ligation and puncture (CLP)-induced sepsis, we found elevated fractalkine mRNA levels in the heart, lung, kidney, and liver, as well as increased plasma levels 24 and 48h after CLP, respectively. In parallel, CLP resulted in a significant downregulation of CX3CR1 mRNA receptor expression in all investigated murine tissues. Septic mice that were pretreated with the selective NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) were found to have a decreased liberation of proinflammtory cytokines such as TNF-α, IL-1ß, IL-6, or IFN-γ. Further PDTC pretreatment attenuated CLP-induced downregulation of CX3CR1 mRNA as well as CLP-induced upregulation of fractalkine mRNA expression in the heart, lung, kidney, liver, and the increase in fractalkine plasma levels of septic mice. In addition, CLP-induced downregulation of renal CX3CR1 protein expression was inhibited by PDTC-pretreatment. Taken together, our data indicate a CLP-induced inverse regulation of the expression between the relating ligand and the receptor with an upregulation of fractalkine and downregulation of CX3CR1, which seems to be mediated by the transcripting factor NF-κB likely via reduced liberation of proinflammtory cytokines in the whole murine organism.

[Aneurysmal subarachnoid hemorrhage]. / Aneurysmatisch bedingte Subarachnoidalblutung.

Acute subarachnoid hemorrhage (SAH) is a severe and acute life-threatening cerebrovascular disease. Approximately 80% of all acute non-traumatic SAHs are the result of a ruptured cerebrovascular aneurysm. Despite advances in diagnosis and treatment a high morbidity and mortality still exists. Apart from the primary cerebral damage there are also secondary complications, such as vasospasm, rebleeding, hydrocephalus, cerebral edema or hydrocephalus. For an appropriate therapy an understanding of the extensive pathophysiology, the options in diagnostics and therapy and the complications of the disease are essential. Anesthesiologists are decisively involved in the therapy of the primary and secondary damages and subsequently in the outcome as well. This article provides an overview of the perioperative and intensive care management of patients with SAH.

[Perioperative Addisonian crisis]. / Perioperative Addison-Krise.

An Addisonian crisis marks an acute adrenocortical failure which can be caused by decompensation of a chronic insufficiency due to stress, an infarct or bleeding of the adrenal cortex and also abrupt termination of a long-term glucocorticoid medication. This article reports the case of a 25-year-old patient with Crohn's disease who suffered an Addisonian crisis with hypotension, hyponatriemia and hypoglycemia during an emergency laparotomy after he had terminated prednisolone medication on his own authority. This necessitated an aggressive volume therapy in addition to an initial therapy with 100 mg hydrocortisone, 8 g glucose and a continuous administration of catecholamines. Under this treatment regimen hemodynamic stabilization was achieved. Reduction of the administration of hydrocortisone after 3 days resulted in cardiovascular insufficiency which required an escalation of the hydrocortisone substitution.