Standardization and Chemical Characterization of Intravenous Therapy in Adult Patients: A Step Further in Medication Safety.

BACKGROUND: Intravenous drug administration is associated with potential complications, such as phlebitis. The physiochemical characteristics of the infusate play a very important role in some of these problems. AIM: The aim of this study was to standardize the dilutions of intravenous drugs most commonly used in hospitalized adult patients and to characterize their pH, osmolarity and cytotoxic nature to better guide the selection of the most appropriate vascular access. METHODS: The project was conducted in three phases: (i) standardization of intravenous therapy, which was conducted using a modified double-round Delphi method; (ii) characterization of the dilutions agreed on in the previous phase by means of determining the osmolarity and pH of each of the agreed concentrations, and recording the vesicant nature based on the information in literature; and (iii) algorithm proposal for selecting the most appropriate vascular access, taking into account the information gathered in the previous phases. RESULTS: In total, 112 drugs were standardized and 307 different admixtures were assessed for pH, osmolarity and vesicant nature. Of these, 123 admixtures (40%), had osmolarity values >600 mOsm/L, pH < 4 or > 9, or were classified as vesicants. In these cases, selection of the most suitable route of infusion and vascular access device is crucial to minimize the risk of phlebitis-type complications. CONCLUSIONS: Increasing safety of intravenous therapy should be a priority in the healthcare settings. Knowing the characteristics of drugs to assess the risk involved in their administration related to their physicochemical nature may be useful to guide decision making regarding the most appropriate vascular access and devices.

Direct hemoperfusion with polymyxin B-immobilized cartridge in severe sepsis due to intestinal perforation: hemodynamic findings and clinical considerations in anticoagulation therapy.

BACKGROUND: High levels of endotoxin have been reported as a risk factor for mortality in critical patients. Toraymyxin® is a column designed to remove circulating blood endotoxin by direct hemoperfusion widely used in Japan. OBJECTIVES: To evaluate the effect of direct hemoperfusion with Toraymyxin® (DHP-PMX) as an adjuvant treatment in patients with severe sepsis due to intestinal perforation in terms of hemodynamic function and coagulation abnormalities. METHODS: Prospective cohort study with a historical control group. Cohort 1: prospective cohort undergoing two sessions of DHP-PMX (n=14). Cohort 2: retrospective historical cohort (n=7). The anticoagulation regime was used according to the protocol of each centre and to the special conditions of each patient. RESULTS: Mean norepinephrine dose was significantly reduced (0.9 ± 0.5 µg/kg/min pre-first DHP-PMX vs 0.3 ± 0.4 µg/kg/min post-second DHP-PMX treatment, p<0.05). Central venous pressure (CVP) and stroke volume variation (SVV) remained without significant changes during the study, as well as cardiac index (CI) in patients with initial CI ≥ 2.5 L/min/m2. CI significantly increased in patients with initial CI<2.5 L/min/m2 (2.1 ± 0.4 pre-first DHP-PMX vs 3.4 ± 0.4 pre-second DHP-PMX session, p=0.01). Mean platelet count pre-first and post-second DHP-PMX decreased significantly (213.9 x 10(3) ± 138.5 x 10(3) platelets/mm3 vs 91.0 x 10(3) ± 53.5 x 10(3) platelets/mm3, p=0.03), without significant changes during each DHP-PMX treatment. Patients did not experience bleeding nor complications derived from DHP-PMX treatments. Survival rates at 28 and 56 days did not differ significantly between cohort 1 and 2 (21.4% vs 42.9%; 42.9% vs 57.1%; respectively). CONCLUSIONS: Performing two sessions of DHP-PMX treatment in a cohort of patients with abdominal sepsis is a feasible adjuvant therapeutic approach, safe in terms of coagulation abnormalities, can be done with different anticoagulation protocols, improves hemodynamic status and may impact on survival.

Estimating kidney function in the critically ill patients.

Glomerular filtration rate (GFR) is an accepted measure for assessment of kidney function. For the critically ill patient, creatinine clearance is the method of reference for the estimation of the GFR, although this is often not measured but estimated by equations (i.e., Cockroft-Gault or MDRD) not well suited for the critically ill patient. Functional evaluation of the kidney rests in serum creatinine (Crs) that is subjected to multiple external factors, especially relevant overhydration and loss of muscle mass. The laboratory method used introduces variations in Crs, an important fact considering that small increases in Crs have serious repercussion on the prognosis of patients. Efforts directed to stratify the risk of acute kidney injury (AKI) have crystallized in the RIFLE or AKIN systems, based in sequential changes in Crs or urine flow. These systems have provided a common definition of AKI and, due to their sensitivity, have meant a considerable advantage for the clinical practice but, on the other side, have introduced an uncertainty in clinical research because of potentially overestimating AKI incidence. Another significant drawback is the unavoidable period of time needed before a patient is classified, and this is perhaps the problem to be overcome in the near future.

Prevalence of acute kidney injury in intensive care units: the "COrte de prevalencia de disFunción RenAl y DEpuración en críticos" point-prevalence multicenter study.

PURPOSE: This study aimed to measure the point prevalence of kidney dysfunction (KD) in the intensive care setting. MATERIALS AND METHODS: A point-prevalence, single-day, prospective study was conducted. Of 919 patients present in 42 Intensive care units (ICUs) for 2 specific days (September 2009 and March 2010), 832 cases were included. Mild KD was defined as a measured creatinine clearance of 90 to 60 mL min(-1) 1.73 m(-2), and severe KD was defined as a creatinine clearance less than 60 mL min(-1) 1.73 m(-2). RESULTS: Prevalence of mild KD was 15.9/100 patients/d (13.5-18.5), and severe KD was 42.4/100 patients/d (39.1-45.8). We considered as having a low probability of experiencing KD those patients without chronic kidney disease, acute kidney injury network stage 0, and a serum creatinine less than 1.2 mg/dL, but among them (557 patients), 18.1% (15.2%-21.6%) had mild KD and 24.2% (20.9%-28%) had severe KD. ICU mortality was 10.6% (7.81%-14.4%) for patients without dysfunction, 16.6% (11.2%-24%) for patients with mild KD, and 29.7% (25.2%-34.7%; P<.001) for patients with severe KD, with a relative risk for severe KD vs no KD of 2.54 (1.90-3.40). In 54.3% patients, at least 1 renal insult was reported. One nephrotoxic drug was administered to 34.4% and 2 or more to 14.9% patients, with a lower frequency among those with chronic kidney disease (30.6% vs 50.8%; P<.05). CONCLUSIONS: Each day of study, more that half of the patients admitted to the ICU showed some derangement in kidney function. More than 25% of patients not fulfilling the KD criteria by serum creatinine or acute kidney injury network showed, in fact, a severe KD, and this finding was associated with higher mortality. More than 50% of the patients admitted to the ICU were subjected to at least 1 renal insult.

Direct hemoperfusion with polymyxin B-immobilized cartridge in severe sepsis due to intestinal perforation: hemodynamic findings and clinical considerations in anticoagulation therapy

Antecedentes. Los niveles altos de endotoxina se han identificado como un factor de riesgo para la mortalidad en pacientes críticos. Toraymyxin® es un cartucho diseñado para eliminar la endotoxina de la sangre circulante por medio de hemoperfusión directa ampliamente utilizado en Japón. Objetivos. Evaluar el efecto de la hemoperfusión directa con Toraymyxin® (HPD-PMX) como tratamiento adyuvante en pacientes con sepsis grave secundaria a perforación intestinal en términos de función hemodinámica y anormalidades de la coagulación. Métodos. Estudio de cohortes prospectivo con un grupo control histórico. Cohorte 1 (n=14): tratada de forma prospectiva con dos sesiones de DHP-PMX. Cohorte 2 (n=7): grupo histórico retrospectivo. El régimen de anticoagulación utilizado fue dejado a libertad de cada centro según práctica local y condiciones especiales de cada paciente. Resultados. La dosis media de noradrenalina se redujo significativamente (0,9 ± 0,5 μg/kg/min antes de la primera hemoperfusión con DHP-PMX vs 0,3 ± 0,4 μg/kg/min tras la segunda, p<0,05). La presión venosa central (PVC) y la variación del volumen sistólico (VVS) permanecieron sin cambios significativos durante el tratamiento, así como el índice cardiaco (IC) en los pacientes con un IC inicial ≥ 2,5 L/min/m2. El IC aumentó significativamente en los pacientes con IC inicial ≤ 2,5 L/min/ m2 (2,1 ± 0,4 antes de la primera hemoperfusión vs 3,4 ± 0,4 tras la segunda sesión, p=0,01). El recuento plaquetario medio descendió significativamente entre antes de la primera sesión y después de la segunda (213,9x103 ± 138,5x103 plaquetas/ mm3 vs 91,0x103 ± 53,5x103 plaquetas/mm3, p=0,03), sin cambios significativos durante cada tratamiento. Los pacientes no experimentaron hemorragias o complicaciones derivadas de los tratamientos con HPD-PMX. La supervivencia al día 28 y día 56 no difirió significativamente entre la cohorte 1 y 2 (21,4% vs. 42,9%; 42,9% vs. 57,1%; respectivamente)...(AU)

Background. High levels of endotoxin have been reported as a risk factor for mortality in critical patients. Toraymyxin® is a column designed to remove circulating blood endotoxin by direct hemoperfusion widely used in Japan. Objectives. To evaluate the effect of direct hemoperfusion with Toraymyxin® (DHP-PMX) as an adjuvant treatment in patients with severe sepsis due to intestinal perforation in terms of hemodynamic function and coagulation abnormalities. Methods. Prospective cohort study with a historical control group. Cohort 1: prospective cohort undergoing two sessions of DHP-PMX (n=14). Cohort 2: retrospective historical cohort (n=7). The anticoagulation regime was used according to the protocol of each centre and to the special conditions of each patient. Results. Mean norepinephrine dose was significantly reduced (0.9 ± 0.5 μg/kg/min pre-first DHP-PMX vs 0.3 ± 0.4 μg/kg/min post-second DHP-PMX treatment, p<0.05). Central venous pressure (CVP) and stroke volume variation (SVV) remained without significant changes during the study, as well as cardiac index (CI) in patients with initial CI≥2.5 L/min/m2. CI significantly increased in patients with initial CI<2.5 L/min/m2 (2.1±0.4 pre-first DHP-PMX vs 3.4 ± 0.4 pre-second DHP-PMX session, p=0.01). Mean platelet count pre-first and post-second DHP-PMX decreased significantly (213.9x103 ± 138.5x103 platelets/mm3 vs 91.0x103 ± 53.5x103 platelets/mm3, p=0.03), without significant changes during each DHP-PMX treatment. Patients did not experience bleeding nor complications derived from DHP-PMX treatments. Survival rates at 28 and 56 days did not differ significantly between cohort 1 and 2 (21.4% vs 42.9%; 42.9% vs 57.1%; respectively)...(AU)

A comparison of the effect of convection against diffusion in hemodynamics and cytokines clearance in an experimental model of septic shock.

BACKGROUND: Replacement therapies based on the use of convection have value for the removal of inflammatory mediators. Such therapies have been proposed for the management of septic shock, but diffusion has not proved useful in this scenario, unless high-flow membranes are used. The exact role of diffusion in these cases remains to be clarified because continuous replacement therapies are usually delivered with low-flow membranes and mixed convection-diffusion modalities. However, studies specifically addressing this problem have not been performed. Our aim was to define the efficacy of hemofiltration (convection) and hemodialysis (diffusion) in cytokine clearance and hemodynamic improvement in an experimental model of septic shock. METHODS: Shock was induced in 15 beagle dogs (weight 10-15 kg) by infusion of 1 mg/kg of ultrapure Escherichia coli lipopolysaccharide diluted in 20 mL saline for 10 minutes. Five animals were followed without interventions (controls), five animals were treated with convection (100 mL kg h) for 6 hours, and five animals were treated with diffusion (100 mL kg h) for 6 hours. RESULTS: All subjects in the control group died during the study, whereas all treated subjects survived. Mean arterial pressure, cardiac output, systolic variability volume, systemic vascular resistances, dPMax, and pulmonary compliance improved in treated subjects. However, the differences in mean arterial pressure and cardiac output were significant only in the convection group and not in the diffusion-treated group.Tumor necrosis factor α rose equally in all groups and decreased only in treated subjects. Interleukin 6 rose in the three groups but decreased only in the convection group and remained unchanged in the control and diffusion groups. CONCLUSION: Convection and diffusion improved survival and hemodynamic parameters in a septic shock model. Improvement was more pronounced with convection, a difference that may be explained by convective clearance of cytokines.

Bladder mucosal CO2 compared with gastric mucosal CO2 as a marker for low perfusion states in septic shock.

Recent reports indicate the possible role of bladder CO(2) as a marker of low perfusion states. To test this hypothesis, shock was induced in six beagle dogs with 1 mg/kg of E. coli lipopolysaccharide, gastric CO(2) (CO(2)-G) was measured with a continuous monitor, and a pulmonary catheter was inserted in the bladder to measure CO(2) (CO(2)-B). Levels of CO(2)-B were found to be lower than those of CO(2)-G, with a mean difference of 36.8 mmHg (P < 0.001), and correlation between both measurements was poor (r(2) = 0.16). Even when the correlation between CO(2)-G and ΔCO(2)-G was narrow (r(2) = 0.86), this was not the case for the relationship between CO(2)-B and ΔCO(2)-B (r(2) = 0.29). Finally, the correlation between CO(2)-G and base deficit was good (r(2) = 0.45), which was not the case with the CO(2)-B correlation (r(2) = 0.03). In our experience, bladder CO(2) does not correlate to hemodynamic parameters and does not substitute gastric CO(2) for detection of low perfusion states.

Validez de la fórmula CKD-EPI para estimar el aclaramiento de creatinina en pacientes ingresados en Cuidados Intensivos / Validity of the CKD-EPI equation to estimate the creatinine clearance in patients admitted to Intensive Care

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Discrepancies in the RIFLE classification are due to the method used to assess the level of derangement of kidney function.

PURPOSE: We hypothesized that RIFLE based on creatinine clearance (CrCl) is superior to that based on serum creatinine (sCr) or Cockroft-Gault (C-G) because it is an earlier marker of kidney dysfunction. MATERIALS AND METHODS: At day 3 of admission, we compared the RIFLE based on sCr, C-G, and CrCl with 28-day mortality and development of RIFLE-F during intensive care unit stay. RESULTS: Percentages in the RIFLE levels were similar for the 3 estimates, but the patients included in each level were different; with CrCl as the reference, κ statistic was 0.29 (95% confidence interval, 0.15-0.43) for sCr and 0.21 (0.07-0.36) for C-G. Mortality at day 28 was 19.3%, with percentages of mortality increasing with RIFLE based in CrCl but not sCr or C-G (area under the curve, 0.57 [45-72] for C-G; 0.57 [44-72] for sCr; and 0.64 [52-79] for CrCl). Logistic regression only showed an independent relationship with mortality for RIFLE measured with CrCl. CONCLUSIONS: RIFLE classification using sCr or C-G at the third day of admission predicts outcome less accurately than with the use of CrCl. Because of the delay in the rise of sCr after a sudden glomerular filtration rate decrease, RIFLE based in CrCl may represent an advantage in terms of precocity.

Seafood intoxication by tetrodotoxin: first case in Europe.

BACKGROUND: Tetrodotoxin is considered the most lethal toxin in the marine environment. Prior cases of intoxication previously described correspond to consumption of tetrodotoxin in tropical or subtropical regions of Asia or the Pacific Islands. OBJECTIVES: We present the first European case of tetrodotoxin intoxication in a patient who ingested part of a trumpet shellfish (Charonia sauliae) from the Atlantic Ocean in Southern Europe. CASE REPORT: Our patient suffered general paralysis, including the respiratory muscles, a few minutes after the consumption of a few grams of C. sauliae. Intubation and mechanical ventilation were necessary for 52 h after the intoxication. The corresponding electrophysiologic studies showed complete non-excitability, with no recordable sensory or motor nerve conduction. We detected the presence of tetrodotoxin in the mollusk and the patient's blood and urine by means of high-performance liquid chromatography-mass spectrometry analysis technique. A previous bioassay showed extremely high quantities of the toxin in the mollusk. CONCLUSIONS: This case alerts us to the possibility of a very harmful biotoxin in European coastal waters. This now should be included in the differential diagnosis of similar cases in Europe, and we must be vigilant for its possible presence in Europe.

Elongación del tronco arterial braquiocefálico sobre los primeros anillos traqueales durante una traqueostomía / Elongation of the brachiocephalic arterial trunk on the first tracheal rings during a tracheostomy

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Planteamientos generales para el mantenimiento del donante de órganos / General planning for the maintenance of the organ donor

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Replacement of 24-h creatinine clearance by 2-h creatinine clearance in intensive care unit patients: a single-center study.

OBJECTIVE: To estimate the usefulness of 2-h creatinine clearance (CrCl) in the ICU and define variables that may reduce agreement. DESIGN: Prospective study. SETTING: Polyvalent ICU of a university hospital. PATIENTS: 359 patients. INTERVENTIONS: We compared 24-h CrCl (CrCl-24h), as the standard measure, with 2-h CrCl (CrCl-2h) (at the start of the period) and the Cockroft-Gault equation (Ck-G). MEASUREMENTS AND RESULTS: The 2-h sample was lost in two patients (0.6%) and the 24-h sample was lost in 50 patients (13.9%). The mean Ck-G was 87.4+/-3.05, with CrCl-2h 109.2+/-4.46 and CrCl-24h 100.9+/-4.21 ml/min/1.73 m2 (r2 of 0.88 for CrCl-2h and 0.84 for Ck-G). The differences from ClCr-24h were 21.8+/-3.3 (p<0.001) for the Ck-G and 8.3+/-2.6 (p<0.05) for CrCl-2h (p<0.05). In the subgroup of patients with CrCl-24h<100 ml/min/1.73 m2, the CrCl-24h value was 52.9+/-2.71 vs. 51.6+/-2.14 for CrCl-2h (p=ns) and 57.6+/-2.56 (p<0.001) for the Ck-G. Patients with CrCl<100 ml/min only showed variability in hyperglycemia during the 24-h period. CONCLUSIONS: In intensive care patients, 24-h CrCl results in a large proportion of non-valid determinations, even under conditions of close monitoring. Two-hour CrCl is an adequate substitute, even in patients who are unstable or who have irregular diuresis where a 24-h collection is impossible. The Cockroft-Gault equation seems less useful in this setting.

Early hemodynamic improvement is a prognostic marker in patients treated with continuous CVVHDF for acute renal failure.

We examined whether hemodynamic improvement after high-flow hemofiltration predicts survival in patients treated with standard continuous renal replacement therapy (CRRT). This was a prospective, observational cohort study of 169 patients, measuring the mean arterial pressure (MAP) and norepinephrine (NE) dosage before and 24 hours after CRRT. Responders were defined as having a 20% reduction in NE dosage or a 20% rise in MAP with no increase in NE, compared with nonresponders. Patients were considered to be unstable if they were receiving NE or their MAP was lower than 60 mm Hg before CRRT. Of the 169 patients, 68% were men; mean age was 53.8 years (52.7 to 54.9), with a mean Acute Physiology and Chronic Health Evaluation (APACHE) II at admission of 21.8 (21.2 to 22.3), of whom 114 were unstable at the start of CRRT. Overall mortality rate 15 days after the end of CRRT was 54.3% (57.7% in stable vs. 52.9% in unstable patients, p = NS). There were 99 responders and 70 nonresponders, the only differences being NE dosage (higher in responders, p < 0.01) and mortality rate (responders 30% vs. nonresponders 74.7%, p < 0.001). In unstable patients, mortality rate was 30% in responders versus 87% in nonresponders (p < 0.001) (72% sensitivity and 86% specificity for predicting death). Logistic regression analysis showed that the only variables associated with death were APACHE II at admission (OR, 1.06; 95% CI, 1.0 to 1.12), percent creatinine decrease (OR, 0.98; CI, 0.96 to 1.0), and lack of hemodynamic response to CRRT (OR, 7.04; CI, 3.3 to 15.02). Hemodynamic improvement after 24-hour CRRT is a strong predictor of survival.