Perioperative care about a patient with multimorbidity.

The assumption of accelerated postoperative recovery according to the ERAS (Enhanced Recovery After Surgery) method is good condition of the patient prepared for surgery and gently operated on. Application of ERAS in postoperative care in the situation of patient with multimorbidity requires an individual approach and greater pre-operative preparation. During the healing process, the operation causes a systemic inflammatory reaction in the body, which is proportional to the size of the surgery trauma. There is fluid movement between the intravascular and interstitial spaces, increased protein catabolism, increased susceptibility to infectious complications and increased risk of decompensation of chronic diseases. The mandatory content of the pre-operative examination is a functional cardiopulmonary reserves assessment, nutritional risk screening, update of diagnostic summary and optimization of chronic medication before surgery. Prehabilitation and nutritional preparation before the planned operation is influenced by the time urgency of the operation, but even in the case of cancer, short-term nutritional preparation is indicated., Medical workplaces are the most suitable for parenteral and enteral pre-operative nutrition however some surgical departments perform the preparation themselves if necessary. The GDT (Goal Directed Therapy) regimen with a higher degree of hemodynamic monitoring and intervention is applied in the postoperative care of hemodynamic unstable risk patients. Next to decompensation of a chronic disease is mainly heart rhythm disorders (most often atrial fibrillation), cardiac complications including coronary event, stroke, acute delirium.

Impact of cumulative fluid balance on the pharmacokinetics of extended infusion meropenem in critically ill patients with sepsis.

BACKGROUND: Meropenem dosing for septic critically patients is difficult due to pathophysiological changes associated with sepsis as well as supportive symptomatic therapies. A prospective single-center study assessed whether fluid retention alters meropenem pharmacokinetics and the achievement of the pharmacokinetic/pharmacodynamic (PK/PD) targets for efficacy. METHODS: Twenty-five septic ICU patients (19 m, 6f) aged 32-86 years with the mean APACHE II score of 20.2 (range 11-33), suffering mainly from perioperative intra-abdominal or respiratory infections and septic shock (n = 18), were investigated over three days after the start of extended 3-h i.v. infusions of meropenem q8h. Urinary creatinine clearance (CLcr) and cumulative fluid balance (CFB) were measured daily. Plasma meropenem was measured, and Bayesian estimates of PK parameters were calculated. RESULTS: Eleven patients (9 with peritonitis) were classified as fluid overload (FO) based on a positive day 1 CFB of more than 10% body weight. Compared to NoFO patients (n = 14, 11 with pneumonia), the FO patients had a lower meropenem clearance (CLme 8.5 ± 3.2 vs 11.5 ± 3.5 L/h), higher volume of distribution (V1 14.9 ± 3.5 vs 13.5 ± 4.1 L) and longer half-life (t1/2 1.4 ± 0.63 vs 0.92 ± 0.54 h) (p < 0.05). Over three days, the CFB of the FO patients decreased (11.7 ± 3.3 vs 6.7 ± 4.3 L, p < 0.05) and the PK parameters reached the values comparable with NoFO patients (CLme 12.4 ± 3.8 vs 11.5 ± 2.0 L/h, V1 13.7 ± 2.0 vs 14.0 ± 5.1 L, t1/2 0.81 ± 0.23 vs 0.87 ± 0.40 h). The CLcr and Cockroft-Gault CLcr were stable in time and comparable. The correlation with CLme was weak to moderate (CLcr, day 3 CGCLcr) or absent (day 1 and 2 CGCLcr). Dosing with 2 g meropenem q8h ensured adequate concentrations to treat infections with sensitive pathogens (MIC 2 mg/L). The proportion of pre-dose concentrations exceeding the MIC 8 mg/L and the fraction time with a target-exceeding concentration were higher in the FO group (day 1-3 f Cmin > MIC: 67 vs 27%, p < 0.001; day 1%f T > MIC: 79 ± 17 vs 58 ± 17, p < 0.05). CONCLUSIONS: These findings emphasize the importance of TDM and a cautious approach to augmented maintenance dosing of meropenem to patients with FO infected with less susceptible pathogens, if guided by population covariate relationships between CLme and creatinine clearance.

[The role of PCSK9-inhibitors and of lipoprotein apheresis in the treatment of homozygous and severe heterozygous familial hypercholesterolemia: A rivalry, or are things quite different?] / Postavení inhibitoru PCSK9 a lipoproteinové aferézy v lécbe homozygotní a závazné heterozygotní familiární hypercholesterolemie: Kdo z koho, nebo je to jinak?

PCSK9-inhibitors belong to the new class of hypolipidemic agents. They enhance catabolism of low density lipoprotein cholesterol (LDL-C) through inhibiting activity of proprotein convertase subtilisin/kexin type 9 (PCSK9). They are monoclonal antibodies (alirocumab, evolocumab etc). Under clinical development are also other types of PCSK9-inhibitors which act at a subcellular level. The treatment with PCSK9-inhibitors can be beneficially combined with lipoprotein apheresis (LA). If such treatment using PCSK9-inhibitors is possible with regard to an individual patients genotype, the combination of LA and PCSK9-inhibitors leads to slowing the space of LDL-C increase between individual procedures of apheresis and enables attaining of the lowest possible values of LDL-cholesterolemia for the longest possible period of time. Due to high efficiency of PCSK9-inhibitors lowering LDL-C, but also their lower cost as compared to therapeutic LA, PCSK9-inhibitors now take precedence over the use of extracorporeal lipoprotein apheresis which, nonetheless, still remains the final method for hypolipidemic treatment of patients with severe hypercholesterolemia, who are resistant to conventional therapy while not reaching the target lipid values and at high cardiovascular risk. They belong to extracorporeal elimination methodologies which remove low density lipoprotein (LDL) cholesterol from circulating blood. LA in combination with higher doses of statins and ezetimib currently represents the most efficient method of treatment of homozygous and statin-refractory heterozygous familial hypercholesterolemia (FH). Residual cardiovascular risk in these patients still remains high, in particular because, despite the aforementioned treatment, the target values for lipids according to present recommendations cannot be reached. The combination of LA with the new drugs is promising, primarily due to its potential for further lowering of LDL-cholesterolemia between the individual apheresis procedures. Preliminary results of the ongoing studies indicate that the new hypolipidemic drugs in combination with LA, or when used separately, will substantially enrich and improve the treatment of refractory FH.Key words: alirocumab - atherosclerosis - evolocumab - hypercholesterolemia - cardiovascular disease - lipoprotein apheresis.

[Position of lipoprotein apheresis in present]. / Postavení lipoproteinové aferézy v soucasnosti.

Lipoprotein apheresis (LA) is an effective treatment method the patients with severe hypercholesterolemia, resistant to the standard therapy. LA is an extracorporeal elimination technique, which specifically removes low density lipoprotein (LDL) cholesterol from the circulation. At present, lipoprotein apheresis, combined with high-dose statin and ezetimibe therapy, is the best available means of treating patients with homozygous and statin refractory heterozygous familial hypercholesterolaemia (FH). However, the extent of cholesterol-lowering achieved is often insufficient to meet the targets set by current guidelines. The recent advent of new classes of lipid-lowering agents provides new hope that the latter objective may now be achievable. These compounds act either by reducing low density lipoprotein (LDL) cholesterol production by inhibiting apolipoprotein B synthesis with an antisense oligonucleotide (mipomersen), or by inhibiting microsomal triglyceride transfer protein (lomitapid), or by enhancing LDL catabolism via monoclonal antibody-mediated inhibition of the activity of proprotein convertase subtilisin/kexin 9 (PCSK9-alirocumab, evolocumab etc). The promising is the combination of LDL-apheresis with new drugs, namely for its potential to further decrease of LDL-cholesterol between apheresis. Depending on the outcome of current trials, it seems likely that these compounds, used alone or combined with lipoprotein apheresis, will markedly improve the management of refractory FH.

[LDL-apheresis in the treatment familial hypercholesterolemia]. / LDL-aferéza v lécbe familiárních hyperlipoproteinemií

LDL-apheresis is an extracorporeal elimination technique, which specifically removes LDL-cholesterol from the circulation. There are six methods for the selective LDL-cholesterol removal these days. The main indications for LDL-apheresis are the diagnosis of homozygous familial hypercholesterolemia, heterozygous familial hypercholesterolemia which is refractory the standard care and intolerance of routine care, and also patients with lipoprotein(a) increase resistant to the farmacotherapy. There is still debate which LDL-cholesterolemia is indication for LDL-apheresis therapy, and the recommendation differs among various countries. Despite large randomized trials are missing, there are several good quality studies to conclude, that the beneficial cardiovascular effects of LDL-apheresis in severe hypercholesterolemia are important and beneficial.

A positive fluid balance does not deteriorate tissue metabolism during fluid resuscitation of sepsis.

OBJECTIVE: Hypovolemia has occurs frequently in sepsis. Due to pathologically increased permeability of the capillaries, the fluid leaks to the interstitium. An adequate fluid therapy is the corner stone to achieve circulatory stabilization and sufficient tissue perfusion; on the other hand, according to the data from the literature a tissue swelling is associated with a risk of deteriorated function of the tissues. The study aimed to examine the effect of a positive fluid balance on muscular metabolism. METHODS: The experimental study employed the model of sepsis in the domestical pig. Ten animals were randomly distributed into a control and a septic group. Sepsis was induced by intravenous administration of E. coli, followed by fluid resuscitation by crystaloids. Microdialysis samples were withdrawn at one-hour intervals for a period of 24 hours and values of lactate, pyruvate, glycerol, and glucose. RESULTS: Pearson's method revealed positive correlations between the lactate/pyruvate ratio and cumulative fluid balance in the septic group (R=0.292, p<0.001) and negative correlations in the control group (R=-0.279, p<0.05). In both groups, however, there was a gradual significant decrease in glycerol values. CONCLUSION: Fluid resuscitation results in positive fluid balance in both septic and control animals. This leads to circulatory stabilization of septic animals, but not a decrease in the anaerobic share of glycolysis. A positive fluid balance in control animals does not result in alteration of muscular aerobic glycolysis. Decreasing glycerol levels in both groups give evidence that a positive fluid balance does not exert a negative impact on cell metabolism.

Pneumocystis pneumonia during medicamentous treatment of Cushing's syndrome--a description of two cases.

Only a few cases of pneumocystis pneumonia (PCP) in Cushing's syndrome have been published in the literature so far. In the majority of these patients, the pneumonia occurred after reduction of the hypercortisolism with medicamentous treatment. We report two cases of PCP during conservative treatment of hypercortisolism. We describe clinical, imaging and laboratory findings in two patients and review published cases of pneumocystits pneumonia in Cushing's syndrome. A 60-year-old woman and 20-year-old man with Cushing's syndrome due to ectopic ACTH syndrome were treated at our department. Both developed pneumocystis pneumonia early after treatment with ketoconazole and ethomidate bromide had been introduced and the levels of cortisol rapidly decreased. PCP prophylaxis in patients with high cortisolemia should be started before treatment of hypercortisolism in current practice. Gradual lowering of plasma cortisol should also reduce the risk of infection by Pneumocystis jiroveci.

Can early postoperative parenteral nutrition have some impact on postoperative inflammatory response intensity?

BACKGROUND AND AIMS: Enhanced recovery after surgery (ERAS) is currently the modern perioperative method of care for improvement of post-surgery patient condition and for minimising various postoperative complications. A question of some negative impact of early postoperative parenteral nutrition on postoperative inflammatory response intensity has not clear-cut answer yet. This pilot project was focused on the possible influence of early parenteral nutrition on the intensity of inflammatory postoperative response to operating trauma in surgical patients. Elected as a model of these conditions were patients with colorectal cancer undergoing major surgery. PATIENTS AND METHODS: 45 patients (of whom 39 were analysed finally) operated for cancer of the large bowel were enrolled into the clinical, prospective, randomized, blinded, and monocentric trial - reference number 201811 S09P of the Ethics committee, University Hospital Hradec Kralove, Czech Republic. Patients were divided into two subgroups according to the type of nutrition: subgroup A - supplemented only with 10% glucose for supported mineral carrier; and subgroup B - supplemented with total parenteral nutrition. Samples of blood and urine were examined immediately after surgery, and on the first, second, and fourth days postoperatively. The inflammatory reaction was monitored by the serum or/and urine concentration of neopterin, tryptophan, and kynurenine, and their urinary ratios with creatinine. The results were analysed by multivariate analysis, and p-values ≤ 0.05 were considered statistically significant. RESULTS: The final total of 39 patients comprised 20 from subgroup A and 19 from subgroup B. The intensity of the inflammatory response detected by the selected inflammatory markers (serum and urine concentrations of neopterin, kynurenine, tryptophan, their serum ratios, and their urinary ratios to creatinine) did not demonstrate statistically significant differences after early administration of the two alternative types of parenteral nutrition. CONCLUSIONS: The results of the study demonstrated the same or a very similar impact on the intensity of postoperative inflammatory response, regardless of whether the patient received intravenous administration of a small simple sugar infusion or total parenteral nutrition during early postoperative care.

Nonbacterial thrombotic endocarditis involving all four cardiac valves.

Nonbacterial thrombotic endocarditis (NBTE) is a well-known complication of hypercoagulable states, particularly in patients with malignancies. Its complications comprise thrombembolism rather than valvular dysfunction. We present a case of a 71-year-old man treated for colonic carcinoma, who died 1 month after tumor resection with clinical signs of respiratory failure. Ante mortem, there was no suspicion of cardiac disease. The autopsy revealed NBTE affecting all four cardiac valves simultaneously, as well as multiple systemic and pulmonary thrombemboli. Microscopically, neither microorganisms nor inflammation were found in the thrombi and/or valve tissues. To the best of our knowledge, this is the fourth case of quadri-valvular NBTE reported in the English-written literature so far.

Covariate determinants of effective dosing regimens for time-dependent beta-lactam antibiotics for critically ill patients.

AIMS: Critically ill patients undergoing aggressive fluid resuscitation and treated empirically with hydrosoluble time-dependent beta-lactam antibiotics are at risk for sub-therapeutic plasma concentrations. The aim of this study was to assess the impact of two covariates - creatinine clearance (Clcr) and cumulative fluid balance (CFB) on pharmacokinetics/pharmacodynamics (PK/PD) target attainment within a week of treatment with meropenem (ME) or piperacillin/tazobactam (PIP/TZB). METHODS: In this prospective observational pharmacokinetic (PK) study, 18 critically ill patients admitted to a surgical Intensive Care Unit (ICU) were enrolled. The primary PK/PD target was free antibiotic concentrations above MIC at 100% of the dosing interval (100%fT>MIC) to obtain maximum bactericidal activity. Drug concentration was measured using liquid chromatography-tandem mass spectrometry. RESULTS: The treatment of both 8 septic patients with IV extended ME dosing 2 g/3 h q8 h and 10 polytraumatized patients with IV intermittent PIP/TZB dosing 4.0/0.5 g q8 h was monitored. 8/18 patients (44%) manifested augmented renal clearence (ARC) where Clcr ≥130 mL/min/1.73 m2. Maximum changes were reported on days 2-3: the median positive CFB followed by the large median volume of distribution: Vdme=70.3 L (41.9-101.5), Vdpip = 46.8 L (39.7-60.0). 100%fTme>MIC was achieved in all patients on ME (aged ≥60 years), and only in two patients (non-ARC, aged ≥65 years) out of 10 on PIP/TZB. A mixed model analysis revealed positive relationship of CFBpip with Vdpip (P=0.021). CONCLUSION: Assuming that the positive correlation between CFB and Vd exists for piperacillin in the setting of the pathological state, then CFB should predict Vdpip across subjects at each and every time point.