Pneumoperitoneum and Acute Kidney Injury-An Integrative Clinical Concept Review.

An increased intraabdominal pressure, particularly when occurring during periods of hemodynamic instability or fluid overload, is regarded as a major contributor to acute kidney injury (AKI) in intensive care units. During abdominal laparoscopic procedures, intraoperative insufflation pressures up to 15 mmHg are applied, to enable visualization and surgical manipulation but with the potential to compromise net renal perfusion. Despite the widely acknowledged renal arterial autoregulation, net arterial perfusion pressure is known to be narrow, and the effective renal medullary perfusion is disproportionately impacted by venous and lymphatic congestion. At present, the potential risk factors, mitigators and risk-stratification of AKI during surgical pneumoperitoneum formation received relatively limited attention among nephrologists and represent an opportunity to look beyond mere blood pressure and intake-output balances. Careful charting and reporting duration and extent of surgical pneumoperitoneum represents an opportunity for anesthesia teams to better communicate intraoperative factors affecting renal outcomes for the postoperative clinical teams. In this current article, the authors are integrating preclinical data and clinical experience to provide a better understanding to optimize renal perfusion during surgeries. Future studies should carefully consider intrabdominal insufflation pressure as a key variable when assessing outcomes and blood pressure goals in these settings.

Mediators of Regional Kidney Perfusion during Surgical Pneumo-Peritoneum Creation and the Risk of Acute Kidney Injury-A Review of Basic Physiology.

Acute kidney injury (AKI), especially if recurring, represents a risk factor for future chronic kidney disease. In intensive care units, increased intra-abdominal pressure is well-recognized as a significant contributor to AKI. However, the importance of transiently increased intra-abdominal pressures procedures is less commonly appreciated during laparoscopic surgery, the use of which has rapidly increased over the last few decades. Unlike the well-known autoregulation of the renal cortical circulation, medulla perfusion is modulated via partially independent regulatory mechanisms and strongly impacted by changes in venous and lymphatic pressures. In our review paper, we will provide a comprehensive overview of this evolving topic, covering a broad range from basic pathophysiology up to and including current clinical relevance and examples. Key regulators of oxidative stress such as ischemia-reperfusion injury, the activation of inflammatory response and humoral changes interacting with procedural pneumo-peritoneum formation and AKI risk will be recounted. Moreover, we present an in-depth review of the interaction of pneumo-peritoneum formation with general anesthetic agents and animal models of congestive heart failure. A better understanding of the relationship between pneumo-peritoneum formation and renal perfusion will support basic and clinical research, leading to improved clinical care and collaboration among specialists.

Reinterpreting Renal Hemodynamics: The Importance of Venous Congestion and Effective Organ Perfusion in Acute Kidney Injury.

The significance of effective renal perfusion is relatively underemphasized in the current literature. From a renal standpoint, besides optimizing cardiac output, renal perfusion should be maximized as well. Among the several additional variables of the critically ill, such as intra-abdominal pressure, the presence of venous congestion and elevated central venous pressures, airway pressures generated by mechanical ventilation do affect net renal perfusion. These forces represent both a potential danger and an ongoing opportunity to improve renal outcomes in the critically ill and an opportunity to move beyond the simplified viewpoint of optimizing volume status. Therefore, to optimize nephron-protective therapies, nephrologists and intensive care physicians should be familiar with the concept of net renal perfusion pressure. This review appraises the background literature on renal perfusion pressure, including the initial animal data and historical human studies up to the most current developments in the field, exploring potential avenues to assess and improve renal blood supply.

Screening for preeclampsia in the first trimester of pregnancy in routine clinical practice in Hungary.

We aimed to evaluate the contribution of different factors in the Fetal Medicine Foundation algorithms for preeclampsia (PE) risk calculation during first-trimester screening in Hungary. We selected subjects for the nested case-control study from a prospective cohort of 2545 low-risk pregnancies. Eighty-two patients with PE and 82 gestational age-matched controls were included. Individual PE risk was calculated using two risk-assessing softwares. Using Astraia 2.3.1, considering maternal characteristics and biophysical parameters only, detection rates (DR) were 63.6% for early-PE and 67.6% for late-PE. When we added placenta associated plasma protein A (PAPP-A) to the risk calculation, DRs decreased to 54.5% and 64.8% respectively. Using Astraia 2.8.2 with maternal characteristics and biophysical parameters resulted in the DRs of 63.6% (early-PE) and 56.3% (late-PE). If we added PAPP-A to the risk calculation, DRs improved to 72.7% and 54.9%. The addition of placental growth factor (PlGF) did not increase detection rates in either calculation. In conclusion, using maternal characteristics, biophysical parameters, and PAPP-A, an acceptable screening efficacy could be achieved for early-PE during first-trimester screening. Since PlGF did not improve efficacy in our study, we suggest setting new standard curves for PlGF in Eastern European pregnant women, and the evaluation of novel biochemical markers.

The value of combined hemodynamic, respiratory and intra-abdominal pressure monitoring in predicting acute kidney injury after major intraabdominal surgeries.

BACKGROUND: The incidence of postoperative acute kidney injury (AKI) is predominantly determined by renal hemodynamics. Beside arterial blood pressure, the role of factors causing a deterioration of venous congestion (intraabdominal pressure, central venous pressure, mechanical ventilation) has emerged. The value of combined hemodynamic, respiratory and intra-abdominal pressure (IAP) monitoring in predicting postoperative acute kidney injury has received only limited exploration to date. METHODS: Data were collected for adult patients admitted after major abdominal surgery at nine Hungarian ICUs. Hemodynamic parameters were compared in AKI vs. no-AKI patients at the time of admission and 48 h thereafter. Regarding ventilatory support, we tested mean airway pressures (Pmean). Effective renal perfusion pressure (RPP) was calculated as MAP-(IAP + CVP + Pmean). The Mann-Whitney U and the chi-square tests were carried out for statistical analysis with forward stepwise logistic regression for AKI as a dependent outcome. RESULTS: A total of 84 patients (34 ventilated) were enrolled in our multicenter observational study. The median values of MAP were above 70 mmHg, IAP not higher than 12 mmHg and CVP not higher than 8 mmHg at all time-points. When we combined those parameters, even those belonging to the 'normal' range with Pmean, we found significant differences between no-AKI and AKI groups only at 12 h after ICU admission (median and IQR: 57 (42-64) vs. 40 (36-52); p < .05). Below it's median (40.7 mmHg) on admission, AKI developed in all patients. If above 40.7 mmHg on admission, they were protected against AKI, but only if it did not decrease within the first 12 h. CONCLUSIONS: Calculated effective RPP with the novel formula MAP-(IAP + CVP + Pmean) may predict the onset of AKI in the surgical ICU with a great sensitivity and specificity. Maintaining effective RPP appears important not only at ICU admission but during the next 12 h, as well. Additional, larger studies are needed to explore therapeutic interventions targeting this parameter.

Renoprotective Postoperative Monitoring: What Is the Best Method for Computing Renal Perfusion Pressure? An Observational, Prospective, Multicentre Study.

BACKGROUND: Low mean arterial pressure (MAP) is a well-known risk factor for postoperative acute kidney injury (AKI), but probably it is not the sole hemodynamic parameter that can influence the development of renal failure. There are data in cardiac patients supporting the role of renal venous congestion in the development of AKI. The aim of our study was to determine a combination of factors best predicting the development of AKI. METHODS: Data were collected prospectively for adult patients admitted after major abdominal surgery to 9 Hungarian intensive care units. Hemodynamic and laboratory parameters were compared in patients with AKI vs. no-AKI at the time of admission. Renal perfusion was computed by different methods from hemodynamic measurements involving MAP, central venous pressure (CVP), intraabdominal pressure (IAP), and mean airway pressures (Pmean). Twelve different, clinically interpretable equations were tested. Statistical evaluation was performed by the Mann-Whitney U test and ROC analysis. RESULTS: Eighty-four patients were enrolled in the study. Renal perfusion pressure was significantly lower in all equations. The equations MAP-IAP-Pmean (1-area under the curve [AUC]: 0.796; likelihood ratio [LR]+: 3.520; LR-: 0.337; p < 0.01), MAP-IAP-CVP-Pmean (1-AUC: 0.794; LR+: 2.743; LR-: 0.282; p < 0.01), and MAP-2 × IAP-CVP-Pmean (1-AUC: 0.791; LR+: 4.321; LR-: 0.262; p < 0.001) showed small to moderate effect on AKI but have better performance than severity score systems (SAPS II [AUC: 0.696; LR+: 3.143, LR-: 0.433; p < 0.01], SOFA [AUC: 0.717; LR+: 2.089; LR-: 0.528; p < 0.001]). CONCLUSION: We found that the best parameter predicting AKI is the MAP-2 × IAP-CVP-Pmean. Further investigation is needed to analyze the role of CVP and Pmean, and to characterize renal venous congestion and tubular pressure more in detail.

Epidemiology of postoperative acute kidney injury in Hungarian intensive care units: an exploratory analysis.

BACKGROUND: The aim of this study was to evaluate the incidence and outcome of postoperative acute kidney injury (AKI) after major noncardiac surgery in Hungarian intensive care units (ICUs). METHODS: We conducted an analysis of a multicenter survey on the epidemiology of AKI in Hungarian ICUs in respect of surgical interventions. The cohort study consisted of all patients (n = 295) over the age of 18 years who were admitted to ICUs after surgery between 1 October 2009 and 30 November 2009. AKI was defined and classified by the acute kidney injury network (AKIN) criteria. RESULTS: Forty-eight (18.1%) patients had AKI during their ICU stay. By AKIN criteria, 27 (10.2%) patients were in stage 1, 11 (4.2%) patients in stage 2, and 10 (3.8%) patients in stage 3. The overall mortality rate of AKI was 39.6% (AKI 1: 25.9%, AKI 2: 40%, and AKI 3: 54.5%; p < 0.001) and the ICU mortality rate was 33.3% (AKI 1: 18.5%, AKI 2: 10%, and AKI 3: 54.5%; p < 0.001). According to logistic regression analysis, age (OR: 1.048; CI: 1.014-1.082; p = 0.005), vasopressor treatment (OR: 9.751; CI: 8.579-10.923; p < 0.001), sepsis (OR: 10.791; CI: 9.353-12.233; p = 0.001), serum-creatinine peak-concentration (OR: 1.035; CI: 1.021-1.047; p < 0.001), and intra-abdominal surgery (OR: 2.558; CI: 1.75-3.366; p = 0.020) were independent predictors for AKI. CONCLUSIONS: The results of this study confirm that there is a high incidence of AKI following major noncardiac surgery, which is associated with higher ICU and in-hospital mortality.

Epidemiology of acute kidney injury in Hungarian intensive care units: a multicenter, prospective, observational study.

BACKGROUND: Despite the substantial progress in the quality of critical care, the incidence and mortality of acute kidney injury (AKI) continues to rise during hospital admissions. We conducted a national, multicenter, prospective, epidemiological survey to evaluate the importance of AKI in intensive care units (ICUs) in Hungary. The objectives of this study were to determine the incidence of AKI in ICU patients; to characterize the differences in aetiology, illness severity and clinical practice; and to determine the influencing factors of the development of AKI and the patients' outcomes. METHODS: We analysed the demographic, morbidity, treatment modality and outcome data of patients (n = 459) admitted to ICUs between October 1st, 2009 and November 30th, 2009 using a prospectively filled in electronic survey form in 7 representative ICUs. RESULTS: The major reason for ICU admission was surgical in 64.3% of patients and medical in the remaining 35.7%. One-hundred-twelve patients (24.4%) had AKI. By AKIN criteria 11.5% had Stage 1, 5.4% had Stage 2 and 7.4% had Stage 3. In 44.0% of patients, AKI was associated with septic shock. Vasopressor treatment, SAPS II score, serum creatinine on ICU admission and sepsis were the independent risk factors for development of any stage of AKI. Among the Stage 3 patients (34) 50% received renal replacement therapy. The overall utilization of intermittent renal replacement therapy was high (64.8%). The overall in-hospital mortality rate of AKI was 49% (55/112). The ICU mortality rate was 39.3% (44/112). The independent risk factors for ICU mortality were age, mechanical ventilation, SOFA score and AKI Stage 3. CONCLUSIONS: For the first time we have established the incidence of AKI using the AKIN criteria in Hungarian ICUs. Results of the present study confirm that AKI has a high incidence and is associated with high ICU and in-hospital mortality.

Recombinant human activated protein C treatment of septic shock syndrome in a patient at 18th week of gestation: a case report.

Recombinant human-activated protein C (rhAPC) has been suggested to treat sepsis. We present the case of a 19-year-old pregnant patient at the 18th week of gestation with septic shock syndrome that originated from urinary tract infection and was successfully treated with rhAPC.

[Ethical regulation of biomedical research in Hungary]. / A biomedicinális kutatások etikai szabályozása Magyarországon.

Hungary joined the Ovideo Treaty (a bioethical health agreement signed by EU countries in 1997), as declared by Law Nr. VI in 2002. In July 1 2002 two departmental orders were enacted: departmental order Nr. [23/2002 (V. 9.)] about the biomedical research in humans and departmental order Nr. [24/2002 (V. 9.)] about the human use and clinical trials of investigational products and the adaptation of Good Clinical Practice (GCP). Both were based on the Health Law. The departmental order on the Medical Research Council [(16/2001 (IV. 28.)] together with these two orders contains the national rules of biomedical research performed in Hungary and also the Hungarian adaptation of various, bioethical principles and directives published by EU or other internationally accepted organisations. According to these regulations from 2002 biomedical research in Hungary could be in agreement with the Oviedo Treaty. Ethical approval and supervision can be obtained from research ethical committees of three types: central, regional and local superimposed upon one another. There are three, central, ethical committees within the frames of the Medical Research Council with national responsibility: Scientific and Research Ethical Committee, Clinical Pharmacological Ethical Committee, Human Reproduction Committee. In some cases regional research ethical committees are entitled to hand out ethical approval and ethical supervision. In those research sites, where the regional research ethical committee is not existent a local committee should be organized for the local ethical control of the research investigations and experiments. This way the ethical requirements and clinical practice by the GCP can be performed in clinical research in Hungary with a special respect to the vulnerable persons possibly involved. The paper gives an overview on recent developments and major ethical principles of the Hungarian biomedical research.