Refractive Outcome After Corneal Lenticule Implantation Ex Vivo Non-Human Study.

PURPOSE: To evaluate changes in corneal refractive parameters after implantation of a stromal lenticule of different thickness. We assume that the refractive outcome depends on the optical power of the used lenticule. METHODS: We conducted an ex-vivo non-human study on 33 normotonic porcine eyeballs divided into two groups, for 4D and 8D human lenticule implantation. Corneal stromal lenticules were obtained as a by-product from a laser procedure ReLEx SMILE. We evaluated corneal refractive parameters measured on Oculus Pentacam© device before and immediately after the intrastromal lenticule implantation. RESULTS: There was no statistically significant difference in corneal refractive parameters between the eyeball groups before lenticule implantation. In both groups, the intrastromal implantation in the depth of 300um led to a significant increase of central corneal pachymetry and corneal anterior steepening. In the 4D group the average central corneal pachymetry increased from 903 ± 124.59 to 1230 ± 148.99 (p = 0.0022) and in 8D group from 733.35 ± 69.60 to 1109 ± 161.64 (p = 0.0008). Induced changes in other studied parameters were not statistically significant, Kmax changed from 45.57 ± 2.78 to 72.07 ± 16.83 (p = 0.0094) and Km front from 40.72 ± 1.60 to 48.87 ± 5.83 (p = 0.0037) in 4D group and in the 8D group average Kmax increased from 42.22 ± 1.54 to 62.95 ± 12.67 (p = 0.0001) and K2 front 40.46 ± 1.64 to 51.51 ± 9.63 (p = 0.0037). There were no significant differences in refractive changes between the 4D and 8D groups after lenticule implantation. CONCLUSION: Intrastromal corneal lenticule implantation induces changes in corneal refractive parameters. In both groups, the implantation induced a significant increase of an anterior corneal steepening without any significant influence on posterior corneal flattening. Corneal lenticule implantation did not lead to any significant change of corneal astigmatism. However, in order to have more precise data for future clinical applications we need to continue with the experiments and verify the results on human corneas.

Mitragyna speciosa (Kratom) poisoning: Findings from ten cases.

Kratom is a mixture of compounds that are present in the leaves of the tropical tree Mitragyna speciosa. It is used as a psychoactive agent with both opiate and stimulant-like effects. In this case series we describe the signs, symptoms, and the management of kratom overdose in the prehospital setting and in intensive care. We retrospectively searched for cases in the Czech Republic. Over 36 months we found 10 cases of kratom poisoning, which healthcare records were analyzed and reported as per CARE guidelines. The dominant symptoms in our series were neurological and included quantitative (n = 9) or qualitative (n = 4) disorder of consciousness. Signs and symptoms of vegetative instability [hypertension (n = 3) and tachycardia (n = 3) vs. bradycardia/cardiac arrest (n = 2), mydriasis (n = 2) vs. miosis (n = 3)] were noticed. Prompt response to naloxone in two cases and lack of response in one patient were observed. All patients survived and the effect of intoxication wore off within two days. Kratom overdose toxidrome is variable and, in keeping with its receptor physiology, consists of signs and symptoms of opioid-like overdose, sympathetic overactivation and serotonin-like syndrome. Naloxone can help to avoid intubation in some cases.

Video Emergency Calls in Medical Dispatching: A Scoping Review.

BACKGROUND: Video emergency calls (VCs) represent a feasible future trend in medical dispatching. Acceptance among callers and dispatchers seems to be good. Indications, potential problems, limitations, and directions of research of adding a live video from smartphones to an emergency call have not been reviewed outside the context of out-of-hospital cardiac arrest (OHCA). OBJECTIVE: The main objective of this study is to examine the scope and nature of research publications on the topic of VC. The secondary goal is to identify research gaps and discuss the potential directions of research efforts of VC. DESIGN: Following PRISMA-ScR guidelines, online bibliographic databases PubMed, Web of Science, SCOPUS, Google Scholar, ClinicalTrials.gov, and gray literature were searched from the period of January 1, 2012 through March 1, 2022 in English. Only studies focusing on video transfer via mobile phone to emergency medical dispatch centers (EMDCs) were included. RESULTS: Twelve articles were included in the qualitative synthesis and six main themes were identified: (1) cardiopulmonary resuscitation (CPR) guided by VC; (2) indications of VCs; (3) dispatchers' feedback and perception; (4) technical aspects of VCs; (5) callers' acceptance; and (6) confidentiality and legal issues. CONCLUSION: Video emergency calls are feasible and seem to be a well-accepted auxiliary method among dispatchers and callers. Some promising clinical results exist, especially for video-assisted CPR. On the other hand, there are still enormous knowledge gaps in the vast majority of implementation aspects of VC into practice.

Non-technical skills in pre-hospital care in the Czech Republic: a prospective multicentric observational study (NTS study).

BACKGROUND: Non-technical skills (NTS) are important for the proper functioning of emergency medical ambulance crews but have hardly been researched in the conditions of clinical pre-hospital care. The primary objective of this study, therefore, is to describe the use of NTS in practice. The secondary objective is to compare if the performance of NTS varies according to the type of case. METHODS: In this multicentric observational study the modified Team Emergency Assessment Measure (TEAM) score was used to assess the performed NTS of two or more crews on site. The evaluation consisted of leadership, teamwork and task management, rated by a field supervisor. The study observations took place in real clinical pre-hospital emergency medical cases when two or more crews were dispatched between October 2019 and August 2020. The sample size was determined by researchers prior to the study to at least 100 evaluated events per each of the three participating emergency medical services. The results are presented as median and interquartile range. The internal reliability, consistency and validity of test items and results were evaluated. The Kruskal-Wallis test and the post hoc Mann-Whitney U test with Bonferroni correction were used for multiple comparisons of three groups. RESULTS: A total of 359 events were evaluated. Surprisingly, the median value for all eight items was as high as 3.0 with a similar interquartile range of 1.0. There were no differences observed by case type (CPR vs. TRAUMA vs. MEDICAL) except from item 1. A post hoc analysis revealed that this difference is in favour of a higher rated performance of non-technical skills in CPR. CONCLUSIONS: The overall result of the performance of non-technical skills can be regarded as very good and can serve for further evaluations. The crews achieved better parameters of NTS in leadership in resuscitation situations in comparison with general medical events. TRIAL REGISTRATION: The study is registered at Clinical Trials under the ID: NCT04503369 .

Pilot implementation of the competence of Czech paramedics to administer sufentanil for the treatment of pain in acute trauma without consulting a physician: observational study.

BACKGROUND: The use of intravenous opioids in the traumatic pain in pre-hospital care in the Czech Republic is based primarily on the indication of a physician. If the paramedic crew arrives at the site earlier or only on their own, analgesia is given after phone-call consultation with the physician or after his arrival at the site. The objective of this study was to evaluate the safety and efficacy of the indication and administration of sufentanil by paramedics in the treatment of pain in acute trauma adult patients without the physician's control. METHODS: Paramedics underwent voluntarily the simulation training aimed at administering intravenously sufentanil to treat pain in acute trauma in adults without physician's indication. Subsequently, the adverse events and efficacy were monitored for a six-month period and compared in two groups: administration of sufentanil by paramedics without this competence, who further consulted the administration by telephone with physicians (group Consultation) and those with this competence (group Competence). RESULTS: A total number of sufentanil administration in group Consultation was 88 and in group Competence 70. There was no respiratory arrest, bradypnea, or need for oxygen therapy reported in any of the study groups. The incidence of nausea was 3% in both groups - Consultation (n = 3) and in Competence (n = 2). Vomiting was not reported in the Consultation group and in 6% in the Competence group (n = 4). Intravenous antiemetic drugs were used in the Consultation group only in 1% (n = 1) and in the Competence group in 7% of patients (n = 5) (p < 0,05). In both groups there was observed a decrease in the pain numeric rating scale (Consultation: M =-3,2; SD = 1,2 points vs. Competence: M =-3,9; SD = 1,8 points). CONCLUSION: Intravenous administration of sufentanil by properly trained paramedics without consultation with a physician in acute trauma can be considered safe.

ABCDE cognitive aid tool in patient assessment - development and validation in a multicenter pilot simulation study.

BACKGROUND: The so called ABCDE approach (Airway-Breathing-Circulation-Disability-Exposure) is a golden standard of patient assessment. The efficacy of using cognitive aids (CA) in resuscitation and peri-arrest situations remains an important knowledge gap. This work aims to develop an ABCDE CA tool (CAT) and study its potential benefits in patient condition assessment. METHODS: The development of the ABCDE CAT was done by 3 rounds of modified Delphi method performed by the members of the Advanced Life Support Science and Education Committee of the European Resuscitation Council. A pilot multicentre study on 48 paramedic students performing patient assessment in pre-post cohorts (without and with the ABCDA CAT) was made in order to validate and evaluate the impact of the tool in simulated clinical scenarios. The cumulative number and proper order of steps in clinical assessment in simulated scenarios were recorded and the time of the assessment was measured. RESULTS: The Delphi method resulted in the ABCDE CAT. The use of ABCDE CAT was associated with more performed assessment steps (804: 868; OR = 1.17, 95% CI: 1.02 to 1.35, p = 0.023) which were significantly more frequently performed in proper order (220: 338; OR = 1.68, 95% CI: 1.40 to 2.02, p < 0.0001). The use of ABCDE CAT did not prolong the time of patient assessment. CONCLUSION: The cognitive aid for ABCDE assessment was developed. The use of this cognitive aid for ABCDE helps paramedics to perform more procedures, more frequently in the right order and did not prolong the patient assessment in advanced life support and peri-arrest care.

Audiovisual Consults by Paramedics to Reduce Hospital Transport After Low-Urgency Calls: Randomized Controlled Trial.

INTRODUCTION: The effect and subjective perception of audiovisual consults (AVCs) by paramedics with a distant physician in prehospital emergency care (PHEC) remain unexplained, especially in low-urgency calls. OBJECTIVES: The primary objective of the study was to evaluate the effect of AVCs by paramedics with a base physician on the rate of patients treated on site without the need of hospital transfer. The co-primary safety outcome was the frequency of repeated ambulance trips within 48 hours to the same patient. Secondary objective was the qualitative analysis of perception of the AVCs. METHODS: During a six-week period, the dispatching center of Karlovy Vary Emergency Medical Service (EMS) randomized low-urgency events from a rural area (n = 791) to receive either a mandatory phone-call consult (PHONE), AVC (VIDEO), or performed by the paramedic crew in a routine manner, when phone-call consultation is for paramedic crew optional (CONTROL). Secondarily, the qualitative analysis of subjective perception of AVCs compared to consultation over the phone by the paramedic and consulting physician was performed. RESULTS: Per-protocol analysis (PPA) was performed (CONTROL, n = 258; PHONE, n = 193; and VIDEO, n = 192) in addition to the intention-to-treat (ITT) analysis. Patients (PPA) in both mandatory consulted groups were twice as likely to be treated and left on site compared to the CONTROL (PHONE: OR = 2.07; 95% CI, 1.19 to 3.58; P = 0.01 or VIDEO: OR = 2.01; 95% CI, 1.15 to 3.49; P = .01). Repeated trips to patients treated and left on site in 48 hours occurred in three (8.6%) of 35 cases in the PHONE group and in eight (23.5%) of 34 cases in the VIDEO group. CONCLUSIONS: The AVCs of the emergency physician by paramedics was not superior to the mandatory conventional phone call in increasing the proportion of patients treated and left at home after a low-urgency call. The AVC improved the subjective feelings of safety by physicians, but not the satisfaction of patients or paramedics, and may lead to an increased need of repeated trips.

Molecular differences in susceptibility of the kidney to sepsis-induced kidney injury.

BACKGROUND: Septic acute kidney injury affects 40-50% of all septic patients. Molecular differences between septic patients with and without acute kidney injury (AKI) are only poorly understood. Here, we investigated gene expression changes that differentiated the subjects who developed septic AKI from those who did not and coupled this approach with traditional parameters of renal physiology. METHODS: In 15 anesthetized, mechanically ventilated and instrumented pigs, progressive sepsis was induced either by peritonitis or by continuous intravenous infusion of Pseudomonas aeruginosa. Animals received standard intensive care including goal-directed hemodynamic management. Analyses were performed on kidneys from sham operated animals, septic pigs without AKI, and pigs with septic AKI. Before, and at 12, 18 and 22 h of progressive sepsis, systemic and renal hemodynamics, cortex microcirculation and plasma IL-6 and TNF-α were measured. At 22 h whole kidney expression of pre-selected genes was analyzed by quantitative Real Time PCR. RESULTS: Animals with septic AKI had systemic hemodynamic phenotype (normo- or hyperdynamic) comparable with non-AKI subjects, but demonstrated higher plasma levels of cytokines, an increase in renal vascular resistance and early fall in cortical microcirculatory blood flow. The genes whose expression discriminated septic AKI from non-AKI included Toll like receptor 4 (up-regulated 2.7-fold, P = 0.04); Cyclooxygenase-2 (up-regulated 14.6-fold, P = 0.01), Angiotensin II Receptor (up-regulated 8.1-fold, P = 0.01), Caspase 3 (up-regulated 5.1-fold, P = 0.02), Peroxisome Proliferator-Activated Receptor Gamma, Coactivator 1 Alpha (down-regulated 2-fold, P = 0.02). CONCLUSIONS: In this preliminary experimental study, kidney gene expression was profoundly different in animals that developed septic AKI as opposed to septic animals that did not. The biological functions of the genes differentially expressed support a role of inflammatory overstimulation coupled with metabolic and apoptotic molecular responses in early septic AKI. Cyclooxygenase-2 and angiotensin type 2 receptor-dependent downstream mechanisms appear fruitful targets for future mechanistic research.

Renal Proteomic Responses to Severe Sepsis and Surgical Trauma: Dynamic Analysis of Porcine Tissue Biopsies.

Although the burden of septic acute kidney injury continues to increase, the molecular pathogenesis remains largely obscure. The aim of this exploratory study was a discovery-driven analysis of dynamic kidney tissue protein expression changes applied for the first time in a classic large mammal model of sepsis. To achieve this goal, analyses of protein expression alterations were performed in serial samples of kidney cortical biopsies (before, 12 and 22 h of sepsis) in mechanically ventilated pigs challenged with continuous infusion of pseudomonas aeruginosa and compared with sham-operated control data. Global protein expression was analyzed using two-dimensional gel electrophoresis and mass spectrometry-based proteomics. Normodynamic sepsis was associated with 43% reduction in glomerular filtration. The exposure to surgical stress per se altered the renal protein expression profile, while sepsis induced distinct and highly dynamic proteome evolution shifting the balance toward cellular distress phenotype. We identified 20 proteins whose expression changes discriminated effects of sepsis from those induced by surgery. The data implicate endoplasmic reticulum stress, oxidative stress, mitochondrial energy metabolism, immune/inflammatory signaling, and tubular transport as major activated pathways. Thus, by coupling the power of sequential tissue proteomics with whole-animal physiological studies, our study helped to establish a first global overview of critical renal proteomic events occurring during surgical trauma and early sepsis in a porcine model. The study supports the notion that multiple potentially subtle and even transient changes in several proteins which are members of key functional interrelated systems appear to play a role in septic acute kidney injury.

Septic shock and chemotherapy-induced cytopenia: effects on microcirculation.

PURPOSE: Neutrophil and platelet activation and their interactions with endothelial cells are considered central features of sepsis-induced microcirculatory alterations. However, no study has evaluated the microvascular pattern of septic shock patients with chemotherapy-induced severe cytopenia. METHODS: Demographic and hemodynamic variables together with sublingual microcirculation recording [orthogonal polarization spectral imaging enhanced by sidestream dark-field technology (OPS-SDF) videomicroscopy] were collected in four groups of subjects: septic shock (SS, N = 9), septic shock in cytopenic patients (NSS, N = 8), cytopenia without infection (NEUTR, N = 7), and healthy controls (CTRL, N = 13). Except for controls, all measurements were repeated after complete resolution of septic shock and/or neutropenia. Video files were processed using appropriate software tool and semiquantitatively evaluated [total vascular density (TVD, mm/mm(2)), perfused vessel density (PVD, mm/mm(2)), proportion of perfused vessels (PPV, %), mean flow index (MFI), and flow heterogeneity index (FHI)]. RESULTS: Compared with controls, there were statistically significant microcirculatory alterations within all tested groups of patients (TVD: SS = 8.8, NSS = 8.8, NEUTR = 9.1 versus CTRL = 12.6, p < 0.001; PVD: SS = 6.3, NSS = 6.1, NEUTR = 6.9 versus CTRL = 12.5, p < 0.001; PPV: SS = 71.6, NSS = 68.9, NEUTR = 73.3 versus CTRL = 98.7, p < 0.001; MFI: SS = 2.1, NSS = 1.9, NEUTR = 2.1 versus CTRL = 3.0, p < 0.05; FHI: SS = 1.0, NSS = 0.9, NEUTR = 0.6 versus CTRL = 0.0, p < 0.001). No significant differences were detected between SS, NSS, and NEUTR groups at baseline. Incomplete restoration of microcirculatory perfusion was observed after septic shock and/or neutropenia resolution with a trend towards better recovery in MFI and FHI variables in NSS as compared with SS patients. CONCLUSIONS: Microvascular derangements in septic shock did not differ between noncytopenic and cytopenic patients. Our data might suggest that profound neutropenia and thrombocytopenia do not render microcirculation more resistant to sepsis-induced microvascular alterations. The role and mechanisms of microvascular alterations associated with chemotherapy-induced cytopenia warrant further investigation.

Tumour necrosis factor-alpha stimulates liver regeneration in porcine model of partial portal vein ligation.

BACKGROUND/AIMS: Portal vein ligation (PVL) could multiply the future liver remnant volume (FLRV). Tumor necrosis factor- alpha (TNF-α) is a pleiotropic cytokine that is connected with initial phase of liver regeneration. The aim of this basic pilot study was to accelerate regeneration of liver parenchyma after PVL. The experimental porcine model was developed to be as much compatible as possible with portal vein embolization (PVE) in human medicine. METHODOLOGY: After ligation of portal branches of caudate and right lateral and right medial liver lobes recombinant porcine TNF-α (TNF-α group) or physiological solution (control group) were applied into non-occluded portal vein branches. The biochemical and immunoanalytical parameters were assessed. The compensatory hypertrophy was evaluated by periodic ultrasonography. The histological examination of liver was performed. RESULTS: The acceleration of growth of hypertrophic liver lobes was maximal at the 7th postoperative day in comparison with the control group (p<0.05); nevertheless this stimulating effect was lost at the end of experiment. The important differences in biochemical or histological studied parametres between study groups were not proved. CONCLUSIONS: The achieved acceleration of growth of hypertrophic liver lobes after application of TNF-α confirms the role of studied cytokine in priming of liver regeneration.

Inhibition of transforming growth factor beta-1 augments liver regeneration after partial portal vein ligation in a porcine experimental model.

BACKGROUND/AIMS: TGF-ß1 is a pleiotropic cytokine that is over expressed in terminal phase of liver regeneration. METHODOLOGY: Twenty-four hours after partial portal vein ligation monoclonal antibody against TGF-ß1 (TGF-ß1 group, 7 piglets) or physiological solution (control group, 9 piglets) were applied into the central venous catheter. The biochemical parameters (bilirubin, urea, creatinine, alkaline phosphatase, gamma- glutamyl transferase, cholinesterase, aspartate aminotransferase, alanine aminotransferase and albumin) were assessed. The compensatory hypertrophy of the non-occluded liver lobes was evaluated by periodic ultrasonography during the next fourteen days and by histological examination. RESULTS: The acceleration of growth of the hypertrophic liver lobes was maximal between 3rd and 7th postoperative days in comparison with the control group (p<0.05). No important differences in the biochemical or studied histological parameters were proved. CONCLUSIONS: The present study describes a new usage of monoclonal antibody against TGF-ß1 in large animal experimental model of partial portal vein ligation.

Searching for mechanisms that matter in early septic acute kidney injury: an experimental study.

INTRODUCTION: In almost half of all sepsis patients, acute kidney injury (AKI) develops. However, the pathobiologic differences between sepsis patients with and without AKI are only poorly understood. We used a unique opportunity to examine dynamic inflammatory, renal hemodynamic, and microvascular changes in two clinically relevant large-animal models of sepsis. Our aim was to assess variability in renal responses to sepsis and to identify both hemodynamic and nonhemodynamic mechanisms discriminating individuals with AKI from those in whom AKI did not develop. METHODS: Thirty-six pigs were anesthetized, mechanically ventilated, and instrumented. After a recovery period, progressive sepsis was induced either by peritonitis (n = 13) or by continuous intravenous infusion of live Pseudomonas aeruginosa (n = 15). Eight sham operated-on animals served as time-matched controls. All animals received standard intensive care unit (ICU) care, including goal-directed hemodynamic management. Before, and at 12, 18, and 22 hours of sepsis, systemic and renal (ultrasound flow probe) hemodynamics, renal cortex microcirculation (laser Doppler), inflammation (interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), oxidative stress (thiobarbituric acid reactive species (TBARS), nitrite/nitrate concentrations (NOx), and renal oxygen kinetics and energy metabolism were measured. RESULTS: In 14 (50%) pigs, AKI developed (62% in peritonitis, 40% in bacteria infusion model). Fecal peritonitis resulted in hyperdynamic circulation, whereas continuous bacteria infusion was associated with normodynamic hemodynamics. Despite insults of equal magnitude, comparable systemic hemodynamic response, and uniform supportive treatment, only those pigs with AKI exhibited a progressive increase in renal vascular resistance. This intrarenal vasoconstriction occurred predominantly in the live-bacteria infusion model. In contrast to AKI-free animals, the development of septic AKI was preceded by early and remarkable inflammatory response (TNF-α, IL-6) and oxidative stress (TBARS). CONCLUSIONS: The observed variability in susceptibility to septic AKI in our models replicates that of human disease. Early abnormal host response accompanied by subsequent uncoupling between systemic and renal vascular resistance appear to be major determinants in the early phase of porcine septic AKI. Nonuniform and model-related renal hemodynamic responses that are unpredictable from systemic changes should be taken into consideration when evaluating hemodynamic therapeutic interventions in septic AKI.

Pharmacokinetic evaluation of voriconazole treatment in critically ill patients undergoing continuous venovenous hemofiltration.

INTRODUCTION: Voriconazole represents an essential part of antimicrobial therapy in critically ill patients. The aim of this study was to exclude a significant alteration in voriconazole pharmacokinetics in critically ill patients undergoing continuous venovenous hemofiltration (CVVH). METHODS: Six patients dependent on CVVH with evidence of an invasive mycotic infection treated with intravenous voriconazole at the standard dosing regimen were investigated. The total serum concentration of voriconazole in arterial blood and the concentration in ultrafiltrate were measured by reverse-phase high-performance liquid chromatography with ultraviolet detection. The authors profiled a 5-point pharmacokinetic concentration-time curve during the 12-hour standard maintenance dosing interval and derived the basic pharmacokinetic parameters. RESULTS: The serum voriconazole concentration did not decrease <1.0 mg/L at any time point, and the mean was 4.3 ± 2.6 mg/L and the median (range) 3.6 (9.0) mg/L. The sieving coefficient of the drug did not exceed 0.30 in any patient (0.22 ± 0.08). The mean serum AUC0-12, the mean total clearance, and the mean clearance via CVVH were 53.52 ± 29.97 mg·h/L [the median (range) of 57.74 (62.34) mg·h/L], 0.11 ± 0.07 L·h-1·kg-1, and 0.007 ± 0.003 L·h-1·kg-1, respectively. The clearance by the CVVH method ranged from 4% to 20% of the total drug clearance. The disposition of voriconazole was not compromised. The mean elimination half-life was 27.58 ± 35.82 hours [the median of 13.10 (92.21) hours], and the mean distribution volume value was 3.28 ± 3.10 L/kg [the median of 2.01 (8.10) L/kg]. Marked variability in serum concentrations, elimination half-life, distribution volume, and total clearance was seen. Half of the patients showed some drug accumulation. CONCLUSIONS: The clearance of voriconazole by CVVH is not clinically significant. In view of this finding, voriconazole dose adjustment in patients undergoing the standard method of CVVH is not required. However, the observed potential for an unpredictable voriconazole accumulation suggests the usefulness for monitoring its levels in critically ill patients.

Plasma and tissue levels of neuropeptide y in experimental septic shock: relation to hemodynamics, inflammation, oxidative stress, and hemofiltration.

Neuropeptide Y (NPY), a potent vasoconstrictor released from the sympathetic nerves, has been suggested to counterbalance sepsis-induced vasodilation. Thus, the changes in plasma and tissue NPY concentrations in relation to hemodynamic variables and inflammatory markers in a porcine model of moderate septic shock were investigated. Susceptibility of NPY to be removed by continuous hemofiltration in two settings has been also studied. Thirty-four domestic pigs were divided into five groups: (i) control group; (ii) control group with conventional hemofiltration; (iii) septic group; (iv) septic group with conventional hemofiltration; and (v) septic group with high-volume hemofiltration. Sepsis induced by fecal peritonitis continued for 22 h. Hemofiltration was applied for the last 10 h. Hemodynamic and inflammatory parameters (heart rate, mean arterial pressure, cardiac output, systemic vascular resistance, plasma concentrations of tumor necrosis factor-α, interleukin-6, and NPY) were measured before and at 12 and 22 h of peritonitis. NPY tissue levels were determined in the left ventricle and mesenteric and coronary arteries. Sepsis induced long-lasting increases in the systemic NPY levels without affecting its tissue concentrations. Continuous hemofiltration at any dose did not reduce sepsis-induced elevations in NPY plasma concentrations, nor did it affect the peptide tissue levels. The increases in NPY systemic levels were significantly correlated with changes in the systemic vascular resistance. The results support the hypothesis of NPY implication in the regulation of the vascular resistance under septic conditions and indicate that NPY clearance rate during hemofiltration does not exceed the capacity of perivascular nerves to release it.

The safety and efficacy of a new anticoagulation strategy using selective in-circuit blood cooling during haemofiltration--an experimental study.

BACKGROUND: Selective in-circuit blood cooling was recently shown to be an effective anticoagulation strategy during short-term haemofiltration. The aim of this study was to examine the safety of this novel method and circuit life. METHODS: Fourteen pigs were randomly assigned to receive continuous haemofiltration with anticoagulation achieved either by selective cooling of an extracorporeal circuit (ECC) (COOL; n = 8) or through systemic heparinization (HEPARIN; n = 6). Before (T0) as well as 1 (TP1) and 6 h (TP6) after starting the procedure the following parameters were assessed: animal status, variables reflecting haemostasis, oxidative stress, inflammation and function of blood elements. RESULTS: All animals remained haemodynamically stable with unchanged body core temperature and routine biochemistry. Regional ECC blood cooling did not alter clinically relevant markers of haemostasis, namely activated partial thromboplastin and prothrombin times, thrombin-antithrombin complexes, von Willebrand factor and plasminogen activator inhibitor-1. Platelet aggregability, serum levels of free haemoglobin, leukocyte count, oxidative burst and blastic transformation of T-lymphocytes were all found to be stable over the treatment period in both groups. ECC blood cooling affected neither plasma malondialdehyde concentrations (a surrogate marker of oxidative stress) nor plasma levels of cytokines (tumour necrosis factor-α, interleukin-6 and -10). While the patency of all circuits treated with systemic heparin was well maintained within the pre-selected period of 24 h, the median filter lifespan in the COOL group was 17 h. CONCLUSION: Utilizing clinically relevant markers, selective in-circuit blood cooling was demonstrated to be a safe and feasible means of achieving regional anticoagulation in healthy pigs. The long-term safety issues warrant further evaluation.

Differential effects of hemofiltration and of coupled plasma filtration adsorption on cardiac repolarization in pigs with hyperdynamic septic shock.

The aim was to investigate effects of continuous hemofiltration (CHF) and of coupled plasma filtration adsorption (CPFA) on electrophysiological properties of the septic heart. Sepsis was induced in anesthetized pigs by fecal peritonitis and continued for 22 h either without intervention (control sepsis) or with intervention (CHF or CPFA) applied for the last 10 h of this period. Electrocardiograms were recorded at baseline, before induction of peritonitis, and 22 h later, at the end of in vivo experiment. In vitro, action potentials were recorded in right ventricular trabeculae. RR, QT, and QTc (QT corrected for heart rate) intervals were shortened by sepsis. Action potential durations (APDs) were shortened by CHF, but not by CPFA, compared with control sepsis. Continuous hemofiltration prolonged APD. Coupled plasma filtration adsorption filtrate did not exert any effect on APD. Plasma separated during CPFA prolonged APD. Continuous hemofiltration shortened cardiac repolarization, and this effect was reversed by the hemofiltrate. In contrast, neither CPFA nor the CPFA filtrate influenced APD. The data indicate that some inflammatory mediators able to delay cardiac repolarization were removed from plasma to hemofiltrate by CHF but not by CPFA.

Reduced L-type calcium current in ventricular myocytes from pigs with hyperdynamic septic shock.

OBJECTIVE: To hypothesize that reduced L-type calcium current with consequent shortening of cardiac repolarization is present in a clinically relevant porcine model of hyperdynamic septic shock. Myocardial depression is a well-recognized manifestation of sepsis and septic shock. Reduction of L-type calcium current was demonstrated to contribute to the myocardial depression in endotoxemic rodents. DESIGN: Laboratory animal experiments. SETTING: Animal research laboratory at a university. SUBJECTS: Twenty-two domestic pigs of either gender. INTERVENTIONS: In anesthetized, mechanically ventilated, and instrumented pigs, sepsis was induced by bacteremia (central venous infusion of live Pseudomonas aeruginosa) and continued for 22 hrs. MEASUREMENTS AND MAIN RESULTS: Electrocardiogram was recorded before and 22 hrs after induction of bacteremia. RR, QT, and QTc intervals were significantly shortened by sepsis. In vitro, action potentials were recorded in right ventricular trabeculae. Action potential durations were shortened in septic preparations. Tumor necrosis factor-alpha did not influence action potential durations. L-type calcium current was measured in isolated ventricular myocytes. Peak L-type calcium current density was reduced in myocytes from septic animals (8.3 +/- 0.4 pA/pF vs. 11.2 +/- 0.6 pA/pF in control). The voltage dependence of both L-type calcium current activation and inactivation was shifted to more negative potentials in myocytes from septic animals. Action potential-clamp experiments revealed that the contribution of L-type calcium current to the septic action potential was significantly diminished. In cardiac myocytes incubated with tumor necrosis factor-alpha, L-type calcium current was not further affected. CONCLUSIONS: In a clinically relevant porcine model, hyperdynamic septic shock induced shortening of ventricular repolarization and reduction of L-type calcium current. The contribution of L-type calcium current to the action potential in septic ventricular myocytes was significantly diminished. Tumor necrosis factor-alpha probably did not contribute to this effect.

Anesthesia and the microcirculation.

There is increasing evidence that the microcirculation and its regulation are severely compromised during many pathological conditions, such as hemorrhage, sepsis, or trauma. The effects of anesthetic agents on macrohemodynamics were investigated intensively in the last several decades. Research regarding modern anesthetics and anesthesia techniques has increased knowledge regarding the nonanesthetic effects of anesthetic agents, including those on organ perfusion and the microcirculation. Alterations in microvascular reactivity, nitric oxide pathways, and cytokine release are presumably the main mechanisms of anesthetic-induced tissue perfusion changes. This review summarizes current methods of microcirculatory status assessment and current knowledge regarding the microcirculatory effects of intravenous and potent volatile anesthetics and anesthesia-related techniques under both normal and pathophysiological conditions.