Haloperidol for preventing delirium in ICU patients: a systematic review and meta-analysis.

OBJECTIVE: Delirium, a common behavioral manifestation of acute brain dysfunction in Intensive Care Unit (ICU), is a significant contributor to mortality and worse long-term outcome. Antipsychotics, especially haloperidol, are commonly administered for the treatment and prevention of delirium in critically ill patients while the evidence for the safety and efficacy of these drugs is still lacking. Therefore, we conducted a systematic review of the benefits of haloperidol for the prevention of delirium in ICU patients. MATERIALS AND METHODS: We made a systematic review and meta-analysis. RESULTS: Eight RCTs with 2806 patients were included. The prophylactic use of haloperidol did not reduce the delirium incidence (RR: 0.90, 95% CI: 0.69-1.71), the duration of delirium (MD: -0.33, 95% CI: -1.25-0.588) and the delirium/coma free days (MD: 0.08, 95% CI: -0.06-0.23). We did not find an increase of extrapyramidal effects (RR: 1.86, 95% CI: 0.30-11.39), QTc prolongation (RR: 1.11, 95% CI: 0.79-1.55) and arrhythmias (RR: 1.26, 95% CI: 0.72-2.19). The use of haloperidol did not increase the ICU (MD: 0.77, 95% CI: -0.28-1.83) and hospital length of stay (MD: -0.57, 95% CI: -1.32-0.18). Haloperidol did not increase the sedation level (RR: 1.88, 95% CI: 0.76-4.63) and mortality (RR: 0.97, 95% CI: 0.83-1.18). CONCLUSIONS: Haloperidol did not reduce the delirium incidence, the delirium duration, the delirium/coma free-days and did not increase the incidence of extrapyramidal effects, arrhythmias, the ICU and hospital length of stays and sedation.

HRV Influence During Renal Transplantation Procedure on Long-Term Mortality.

BACKGROUND: The autonomic nervous system plays an important role in heart function regulation. One of the most acknowledged methods for noninvasive measurement of autonomic system activity is to determine heart rate variability (HRV). Reduced HRV parameters-heart rate rigidity/stiffness-are an independent prognostic factor of sudden cardiac death risk because of arrhythmia. Renal transplantation is an important factor in HRV changes because of hemodynamic and ion disturbances. The main purpose of this study was to determine the influence of HRV disturbances during renal transplantation procedures on long-term mortality in patients with chronic kidney disease. METHODS: A prospective observation study was performed in the Department of Anesthesiology, Intensive Care, and Acute Poisoning, Pomeranian Medical University, Szczecin, Poland. There were 75 patients (mean age, 47 ± 12 years; 42 men) treated with renal transplantation between 2008 and 2010. Patients were monitored with electrocardiographic tracing with the use of 7 electrodes in position type B. The final stage of analysis was to determine the possible relationship between HRV parameters during the perioperative period and the number of deaths within a 5-year follow-up. RESULTS: HRV parameters during the perioperative period of renal transplantation and the number of deaths within a 5-year follow-up, measured by use of the Holter method, did not differ among patients in the studied population. CONCLUSIONS: HRV is a noninvasive and confirmed tool used for the evaluation of autonomic function and mortality risk in patients with end-stage renal disease. HRV parameters recorded in the perioperative period are not optimal stratification tools for estimating the risk of cardiac deaths in patients with end-stage renal disease.

Influence of the hemodynamic status of multiorgan donors on long-term kidney graft survival--a multivariable analysis.

BACKGROUND: The quality of transplanted organ and timing of the initiation of its effective function depends on many factors potentially causing graft dysfunction. The aim of this study was to evaluate the influence of the cardiovascular status of multiorgan donors on the long-term kidney graft survival over a 15-year observation period. METHODS: In 2007, the authors of this study published a multicenter prospective study evaluating the influence of the hemodynamic status of multiorgan donors on the early function of transplanted kidney. The results of that study showed that mean arterial pressure, central venous pressure, and pulmonary capillary wedge pressure values of the donor importantly influence the frequency of delayed graft function after renal transplantation. The present analysis covers the effect of the donor's hemodynamic status parameters on graft function time within the 15-year observation period. Univariate and multivariate analyses using the Cox regression proportional hazard model were performed to evaluate the prognostic parameters for overall survival and renal graft survival time. P < .05 was considered to be significant. RESULTS: The univariate analysis showed a significantly shorter time of graft survival in the group of recipients who had a kidney retrieved from donors with lower pulmonary capillary wedge pressure values (P = .038) and lower cardiac index values (P = .039). The same results were obtained for the multifactorial Cox logistic regression analysis. CONCLUSIONS: The filling of the intravascular bed of the donor as determined by pulmonary capillary wedge pressure and maintained donor tissue perfusion as determined by cardiac index, impose important factors influencing long-term kidney graft survival.

Influence of selected factors on long-term kidney graft survival--a multivariable analysis.

BACKGROUND: Long-term function of transplanted kidney is the factor determining quality of life for transplant recipients. The aim of this study was to evaluate the effect of selected factors on time of graft function after renal transplantation within 15 years of observation. METHODS: Preoperative and intraoperative factors were analyzed in 232 kidney recipients within a 15-year observation period. Analysis included age, sex, cause of recipient's renal failure, length of hemodialyses before transplantation, peak panel reactive antibodies test, human leukocyte antigen compatibility, cold ischemia time, delayed graft function occurrence, length and time of hemodialyses after transplantation, early graft rejection, creatinine level at days 1, 3, 7, 30, 90, and 180 after transplantation, and influence of these factors on the time of graft function. Statistical analysis was performed with the use of univariate and multivariate Kaplan-Meier test and Cox regression proportional hazards model, with P < .05 considered to be significant. RESULTS: Univariate analysis showed significantly shorter renal graft function in the group of recipients with higher creatinine levels in all of the analyzed time periods and in patients experiencing delayed graft function. Length of time of hemodialyses after transplantation and number of dialyses had significant impact on worsening of late transplant results. Multivariate analysis reported that early graft rejection in the postoperative period is an independent factor improving late graft function: P = .002; hazard ratio (HR), 0.49 (95% confidence interval [CI], 0.31-0.78). Higher creatinine level at day 90 after kidney transplantation is a predictive factor of late graft dysfunction: P = .002; HR, 1.68 (95% CI 1.2-2.35). CONCLUSIONS: Creatinine level at day 90 after renal transplantation is the prognostic factor of long-term kidney function. Early transplant rejection leads to introduction of more aggressive immunosuppression protocol, which improves long-term transplant results.

Effect of recipient sensitization (peak panel reactive antibodies) on 15-year survival after kidney transplantation.

BACKGROUND: Despite dynamic development within the field of transplantology, the immunization of a potential organ recipient remains an important issue for transplant teams. Panel reactive antibodies (PRA) identification in the serum of the recipient remains routine practice in the majority of transplantation centers. The influence of peak PRA levels on graft function is a well known fact. The aim of this study was to determine the effect of peak PRA on long-term survival after renal transplantation. METHODS: The study was conducted on a group of 232 kidney recipients from multiorgan donors, transplanted in 6 transplant centers in Poland from 1995 to 1997. Data analyzed in this study included recipients' age, sex, PRA, HLA, number and time of hemodialyses after the transplantation, cold ischemia time, and etiology of end-stage renal disease. The effect of data examined in this study on mortality was evaluated at set time points at 5, 10, and 15 years after transplantation. The statistical methods included monofactorial and multifactorial Kaplan-Meier survival analysis and Cox proportional hazards model for mortality prediction. A P value of <.05 was considered to be statistically significant. RESULTS: Among all of the analyzed factors, only peak PRA concentrations significantly correlated with increased mortality among renal transplant recipients. The results were analyzed in all of the set time points: P = .007 at 5 years, P = .014 at 10 years, and P = .05 at 15 years after transplantation. CONCLUSIONS: The increased level of PRA in kidney recipients is a risk factor increasing mortality after the transplantation.

Impact of graft infection on long-term survival after kidney transplant.

BACKGROUND: Patients undergoing transplantation procedures are at a high risk of developing infections because of the need for immunosuppression. Infections presenting directly after renal transplantation greatly influence the overall success of the procedure. The aim of this study was to evaluate the influence of postoperative infection on the length of survival after renal transplant. METHODS: In 2009 a multicenter prospective trial evaluating the factors that influence the occurrence of postoperative infective complications was published by the authors. That study reported that 25 out of 232 recipients of a renal transplant were diagnosed with an infection. The present study shows the effect of postoperative infection on the length of survival after renal transplantation during a 15-year observation period. Statistical methods involved monofactorial and multifactorial Kaplan-Meier analysis for the length of survival and the Cox proportional hazards model for mortality prediction. A P value of <.05 was considered to indicate statistical significance. RESULTS: The analysis demonstrated that the lifespan of renal transplant recipients was decreased in those with postoperative infection, at both year 10 of the observation period (P = .013) and 15 years after transplantation (P = .012). Moreover, it was ascertained that an infection in the postoperative period was an independent risk factor increasing the mortality after renal transplantation: P = .026; hazard ratio 2.90 (95% confidence interval, 1.13-7.41). CONCLUSIONS: The occurrence of an infection in the postoperative period significantly decreases the lifespan of a renal transplantation recipient.

Donor-recipient gender mismatch affects early graft loss after kidney transplantation.

BACKGROUND: We sought to determine the risk factors influencing the occurrence of early graft loss among kidney transplant recipients. STUDY DESIGN: One hundred forty-six potential donors and 230 kidney recipients were included in the study. Prior to organ procurement we collected demographic data as well as hemodynamic data of mean arterial pressure, central venous pressure, pulmonary capillary wedge pressure, systemic vascular resistance index acquired by means of a thermodilution method. The recipient data included age, gender, prior hemodialysis period, panel-reactive antibodies, cold ischemia time, renal insufficiency cause, and donor-recipient gender mismatch. We assessed the influence of the data on graft loss at 30 days after renal transplantation. To confirm the relationships, we performed statistical analyses using chi-square, Fisher exact, and V. Cramer tests. RESULTS: There were no significant relationships between the analyzed parameters and early graft loss in the study group except for gender mismatch. The 71 female recipients of male kidneys showed the lowest graft survival: donor/recipient male/female 89%; donor/recipient female/male 97%; no mismatch 97% (P=.01). CONCLUSIONS: Female recipients of male kidneys may experience a greater risk of early graft loss compared with all other gender combinations.

Association of rs10918594 polymorphisms of nitric oxide synthase 1 adaptor protein (NOS1AP) with QTc interval prolongation during kidney transplantation.

BACKGROUND: The mechanisms of sudden cardiac death are difficult to recognize, but repolarization disturbances have been shown to be the cause. The purpose of this study was to investigate whether the polymorphism of nitric oxide synthase 1 adaptor protein (NOS1AP) was related to the risk of occurrence of corrected QTc-interval prolongation and ventricular arrhythmias recorded on electrocardiography (ECG) Holter monitoring in kidney transplant recipients. STUDY DESIGN: The 75 adult first kidney transplant patients included 43 men with an overall mean age of 45±12 years (range, 20-68). Additional patient monitoring during the procedure and in the postoperative period consisted of a continuous ECG tracing recording and investigation of the rs10918594 NOS1AP polymorphism. RESULTS: We observed Transient QTc-interval prolongation during the perioperative period. NOS1AP genotypes were in Hardy-Weinberg equilibrium. For further statistical analysis, we combined GG homozygotes and CG heterozygotes because of the small numbers available; therefore, only a dominant mode of inheritance was investigated. There were no gender differences in QTc-interval patterns. Analysis of variance with repeated measures revealed no interaction between NOS1AP and QTc-interval values taken at various times among the kidney recipients. CONCLUSIONS: The transplantation procedure may lead to dynamic repolarization disturbances, which may produce an increased risk of severe arrhythmias despite optimization of patient status. The NOS1AP rs203462 polymorphisms did not correlate with an increased risk of QT interval prolongation among kidney recipients.

Graft infection in kidney recipients and its relation to transplanted kidney function.

INTRODUCTION: Following kidney transplantation, septic complications are the leading causes of therapeutic failure including recipient death or graft removal. The serum creatinine level is one of the earliest metrics of kidney metabolic function. We examined the influence of graft infection on serum creatinine levels in kidney recipients. STUDY DESIGN: We analyzed the function of 220 kidneys transplanted in nine centers in Poland. The kidneys were recovered from 146 multiorgan donors. Donor urea and creatinine levels were within the normal range. We investigated the influence of perioperative graft infection incidence on recipient creatinine levels at 1, 2, 3, 7, 14, 30, 90, and 180 days after kidney transplantation. The association of the serum creatinine level with categorical variables was assessed using either Student t test analysis of variance and multivariate techniques. In all analyses P<.05 indicated statistical significance. RESULTS: There were 25 graft infections revealing a significant relationship with increased recipient serum creatinine level after kidney transplantation (P=.003). Multivariate analysis confirmed the impact of infection. CONCLUSION: Perioperative kidney graft infection influenced graft funtion in the early and late periods post-transplantation.

Cause of death in multiorgan donors and its relation to the function of transplanted kidneys.

BACKGROUND: Brain death is an important variable contributing to donor-specific kidney damage. Poor kidney performance posttransplantation may be related to the cause of death of the donor. OBJECTIVE: To assess the influence of cause of death in multiorgan donors on the function of transplanted kidneys. MATERIAL AND METHODS: Standard criteria for the brain stem death protocol were applied in 146 potential heart donors included in the study. Conventional supportive management consisted of mechanical ventilation to achieve normocapnia, rewarming, and fluid and electrolyte replacement. Dopamine infusion not exceeding 10 microg/kg/min and desaminovasopressin were titrated to predetermined mean arterial pressure (MAP). In renal allograft recipients (n = 232), kidney function was monitored using serial serum creatinine concentrations on days 1, 2, 3, 7, 14, 30, and 90 posttransplantation. The relation between donor cause of death (injury, bleeding, or other cause) and recipient serum creatinine concentration was analyzed in the postoperative period. RESULTS: Significantly greater serum creatinine concentrations were observed up to 14 days posttransplantation in recipients of a kidney from a donor who died of any cause other than injury. Recipients of a kidney from a donor who died of bleeding exhibited significantly greater serum creatinine concentrations at 30 days posttransplantation. CONCLUSIONS: A cause of death other than injury or bleeding in a multiorgan donor is predictive of worse kidney graft function in the first 14 days posttransplantation. Intracranial bleeding in a multiorgan donor is predictive of worse kidney graft function in the early period posttransplantation.

Association of the A1936G (rs203462) of A-kinase anchoring protein 10 polymorphisms with QT interval prolongation during kidney transplantation.

INTRODUCTION: The purpose of this study was to investigate whether the polymorphism in the kinase-binding domain of A-kinase anchoring protein 10 (AKAP10) was related to the risk of occurrence of potentially dangerous arrhythmias during kidney transplant. METHODS: We performed this prospective observational study with additional patient monitoring during the kidney transplant procedure and in the postoperative period with continuous electrocardiogram (ECG) - (digital holter; ECG monitor type 300-7 Suprima system; Oxford, UK). After manual trace analysis, we performed classification of arrhythmias by interval measurement (including QT correction according to Bazett's formula: Qtc = QT/RR1/2), ST segment analysis within all channels, and analysis of heart rate variability (HRV) parameters (time analysis: SDNN as total rate variability measure, SDANN as long-term variability measure, SDNNindex, rMSSD and pNN50 as short-term variability measure) as well as frequency measure of power width parameters in the spectrum between 0.0033 Hz and 0.4 Hz. Subsequently applying polymerase chain reaction restriction fragment length polymorphism methods, we investigated A1936G (rs203462) AKAP10 polymorphism among 54 kidney recipients. RESULTS: Analysis of variance showed that prolongation of the QTc interval associated with the variant genotypes (GG + AG) was significantly greater compared with the AA genotype among kidney recipients (P = .04). We did not observe a relationship between the AKAP10 polymorphism and other arrhythmias, or clinical or environmental factors. CONCLUSIONS: Our data suggested that the AKAP10 (rs203462) GG + AG variation was associated with an increased risk of severe arrhythmias during kidney transplantation.

Risk factors for septic complications in kidney transplant recipients.

INTRODUCTION: Septic complications following kidney transplantation are a leading cause of therapeutic failure. An early diagnosis may protect the recipient from the severe consequences of sepsis. We sought to determine the risk factors influencing the occurrence of septic complications among kidney transplant recipients. MATERIALS AND METHODS: The 146 potential donors included in the study were evaluated for brain stem death criteria. Supportive management included mechanical ventilation to normocapnia, rewarming, as well as fluid and electrolyte replacement. Dopamine infusions and desaminovasopressin were titrated to predetermined mean arterial pressure (MAP). Central venous pressure (CVP) was maintained at 8 to 11 mm Hg. Hemodynamic data were acquired by the thermodilution method prior to organ procurement: MAP, CVP, pulmonary capillary wedge pressure (PCWP), and systemic vascular resistance index (SVRI). Recipient data included age, gender, period of prior hemodialysis, panel reactive antibodies, cold ischemia time, and cause of renal insufficiency. The 232 kidney recipients were examined for occurrence of septic complications including septicemia, pneumonia, peritonitis, or graft infection. RESULTS: Kidney transplants from donors with MAP < 70 mm Hg and SVRI < 1200 dyne x s/cm(5) x m(2) showed a significantly higher occurrence of septic complications in recipients (P < .05) where mortality rate was also significantly greater (P < .01). CONCLUSIONS: MAP < 70 mm Hg and SVRI < 1200 dyne x s/cm(5) x m(2) among organ donors predicted greater occurrence of septic complications and increased mortality among kidney transplant recipients.