Clinical practice guidelines for evidence-based management of sedoanalgesia in critically ill adult patients.

INTRODUCTION: Optimal management of sedation, analgesia and delirium offers comfort and security for the critical care patient, allows support measures to be applied more easily and enables an integral approach of medical care, at the same time that lowers the incidence of complications, wich translates in better patient outcomes. OBJECTIVE: To update the Guía de práctica clínica basada en la evidencia para el manejo de la sedoanalgesia en el paciente adulto críticamente enfermo published in Medicina Intensiva in 2007, and give recommendations for the management of sedation, analgesia, and delirium. METHODOLOGY: A group of 21 intensivists from 9 countries of the Federación Panamericana e Ibérica de Sociedades de Medicina Crítica y Terapia Intensiva, 3 of them also specialists in clinical epidemiology and methodology, gathered for the development of guidelines. Assessment of evidence quality and recommendations were made based on the Grading of Recommendations Assessment, Development and Evaluation system. Strength of recommendations was classified as 1=strong, or 2=weak, and quality of evidence as A=high, B=moderate, or C=low. Two authors searched the following databases: MEDLINE through PUBMED, The Cochrane Library and Literatura Latinoamericana y del Caribe en Ciencias de la Salud and retrieved pertinent information. Members assigned to the 11 sections of the guidelines, based on the literature review, formulated the recommendations, that were discussed in plenary sessions. Only those recommendations that achieved more than 80% of consensus were approved for the final document. The Colombian Association of Critical Medicine and Intensive Care (AMCI) supported the elaboration of this guidelines. RESULTS: Four hundred sixty-seven articles were included for review. An increase in number and quality of publications was observed. This allowed to generate 64 strong recommendations with high and moderate quality of evidence in contrast to the 28 recommendations of the previous edition. CONCLUSIONS: This Guidelines contains recommendations and suggestions based on the best evidence available for the management of sedation, analgesia and delirium of the critically ill patient, including a bundle of strategies that serves this purpose. We highlight the assessment of pain and agitation/sedation through validated scales, the use of opioids initially to apropiate analgesic control, associated with multimodal strategies in order to reduce opioide consumption; to promote the lowest level of sedation necessary avoiding over-sedation. Also, in case of the need of sedatives, choose the most appropiate for the patient needs, avoiding the use of benzodiazepines and identify risk factors for delirium, in order to prevent its occurrence, diagnose delirium and treat it with the most suitable pharmacological agent, whether it is haloperidol, atypical antipsychotics or dexmedetomidine, once again, avoiding the use of benzodiazepines and decreasing the use of opioids.

Rabbit skeletal muscle PO2 during hypodynamic sepsis.

We measured skeletal muscle tissue PO2 (PtO2) in anesthetized rabbits (n = 7) following infusion of an intravenous bolus of E coli endotoxin. An array of surface PO2 microelectrodes was placed over the hindlimb biceps femoris muscle and sufficient readings were obtained to construct a PtO2 histogram. Changes in the histogram standard deviation were used to characterize micro-circulatory maldistribution. Systemic O2 consumption (VO2) was measured by the expired gas method. Cardiac output (Q) and systemic O2 transport (TO2) were calculated. Samples of arterial, right atrial (ra), and hindlimb venous blood, from a catheter placed in the infrarenal portion of the vena cava, were simultaneously obtained for measurement of blood gases and saturations. Following the administration of endotoxin, there were decreases in Q and TO2 of approximately 50 percent. The VO2 initially decreased 23 percent, but returned to baseline levels 30 minutes after endotoxin administration. Systemic O2 extraction ratio (ERO2 = VO2/TO2) increased from 0.32 +/- .03 to 0.54 +/- .07 (p less than 0.01), whereas hindlimb ERO2 increased from 0.42 +/- .03 to 0.60 +/- .02 (p less than 0.01). The arithmetic mean of the PtO2 histograms decreased after endotoxin infusion (43 +/- 4 to 7 +/- 2 mm Hg; p less than 0.01), but PLO2 remained at baseline levels (35 +/- 2 vs. 33 +/- 2 mm Hg; p = NS). The standard deviation of the PtO2 histograms remained constant during the experiment. This finding supports the notion that skeletal muscle microcirculatory heterogeneity does not increase during endotoxin induced hypodynamic sepsis.

Effects of hemorrhage on gastrointestinal oxygenation.

OBJECTIVES: (1) To demonstrate that metabolic parameters are better indicators of tissue hypoxia than regional and whole oxygen consumption (VO(2)). (2) To compare intramucosal pH (pHi) in different gastrointestinal segments. DESIGN: Prospective, interventional study. SETTING: Research laboratory at a university center. SUBJECTS: Fourteen anesthetized, mechanically ventilated dogs. INTERVENTIONS: Twenty milliliters per kilogram bleeding. MEASUREMENTS AND MAIN RESULTS: We placed pulmonary, aortic and mesenteric venous catheters, and an electromagnetic flow probe in the superior mesenteric artery, and gastric, jejunal and ileal tonometers to measure flows, arterial and venous blood gases and lactate, and intramucosal PCO(2). We calculated systemic and intestinal oxygen transport (DO(2)) and consumption (VO(2)), pHi and arterial minus intramucosal PCO(2) (DeltaPCO(2)). Then, we bled the dogs and repeated the measurements after 30 min. Systemic and intestinal DO(2) fell (26.0+/-7.3 versus 8.9+/-2.6 and 71.9+/-17.3 versus 24.6+/-9.6 ml/min per kg, respectively, p<0.0001). Systemic and intestinal VO(2) remained unchanged (5.5+/-1.3 versus 5.4+/-1.3 and 15.7+/-5.0 versus 14.9+/-5.3 ml/min per kg, respectively). Gastric, jejunal and ileal pHi (7.13+/-0.11 versus 6.96+/-0.17, 7.18+/-0.06 versus 6.97+/-0.15, 7.12+/-0.11 versus 6.94+/-0.14, p<0.05) and DeltaPCO(2) (21+/-13 versus 35+/-23, 15+/-5 versus 33+/-16, 23+/-17 versus 38+/-20, p<0.05) changed accordingly. Arterial and mesenteric venous lactate and their difference, rose significantly (1.7+/-0.9 versus 3.7+/-1.4 and 1.8+/-0.8 versus 4.3+/-1.5 mmol/l, 0.1+/-0.6 versus 0.6+/-0.7 mmol/l, p<0.05). CONCLUSIONS: During hemorrhage, systemic and intestinal VO(2) remained stable. However, hyperlactatemia and intramucosal acidosis evidenced anaerobic metabolism. pHi changes paralleled in the three intestinal segments.

End-tidal CO2 pressure determinants during hemorrhagic shock.

OBJECTIVES: To examine the relationship between end-tidal CO2 (PETCO2) and its physiological determinants, pulmonary blood flow (cardiac output, CO) and CO2 production (VCO2), in a model of hemorrhagic shock during fixed minute ventilation. DESIGN AND SETTING: Prospective, observational study in a research laboratory at a university center. SUBJECTS AND INTERVENTIONS: Six anesthetized, intubated, and mechanically ventilated mongrel dogs. Progressive stepwise bleeding. MEASUREMENTS AND RESULTS: We continuously measured PETCO2 with a capnograph, pulmonary artery blood flow with an electromagnetic flow probe, arterial oxygen saturation (SaO2) with a fiberoptic catheter, and oxygen consumption (VO2) and VCO2 by expired gases analysis. Oxygen delivery (DO2) was continuously calculated from pulmonary blood flow and SaO2. We studied the correlation of PETCO2 with CO and VCO2 in each individual experiment. We also calculated the critical point in the relationships PETCO2/ DO2 and VO2/DO2 by the polynomial method. As expected, PETCO2 was correlated with CO. The best fit was logarithmic in all experiments (median r2 = 0.90), showing that PETCO2 decrease is greater in lowest flow states. PETCO2 was correlated with VCO2, but the best fit was linear (median r2 = 0.77). Critical DO2 for PETCO2 and VO2 was 8.0 +/- 3.3 and 6.3 +/- 2.5 ml x min(-1) kg(-1), respectively (NS). CONCLUSIONS: Our data reconfirm the relationship between PETCO2 and CO during hemorrhagic shock. The relatively greater decrease in PETCO2 at lowest CO levels could represent diminished CO2 production during the period of VO2 supply dependency.

[Prognosis for acute exacerbation of chronic obstructive pulmonary disease in mechanically ventilated patients]. / Pronóstico de los enfermos con enfermedad pulmonar obstructiva crónica reagudizada que precisan ventilación mecánica.

OBJECTIVE: To determine the variables associated with prognosis for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in mechanically ventilated patients. DESIGN: Prospective cohort study with retrospective analysis. LOCATION: 361 Intensive Care Units (ICU) in 20 countries. PATIENTS AND METHODS: There were included in the study 522 patients who required mechanical ventilation for more than 12 hours due to an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). In order to determine those variables associated with mortality, there was performed a recursive partition analysis in which the following variables were included: demographics, arterial blood gas prior to intubation, complications arising during mechanical ventilation (barotrauma, acute respiratory distress syndrome, ventilator-associated pneumonia, sepsis), organ dysfunction (cardiovascular, renal, liver, coagulation) and duration of ventilatory support. INTERVENTIONS: None. VARIABLES OF PRIME IMPORTANCE: ICU mortality. RESULTS: ICU and hospital mortality rates were 22% and 30%, respectively. Variables associated with mortality were cardiovascular dysfunction, renal dysfunction and duration of ventilatory support > 18 days. Median durations were as follows: mechanical ventilatory support, 4 days (P25: 2, P75: 6); weaning from ventilatory support, 2 days (P25: 1, P75: 5); stay in intensive care unit, 8 days (P25: 5, P75: 13); stay in hospital, 17 days (P25: 10, P75: 27). CONCLUSIONS: Mortality in the studied cohort of patients with AECOPD was associated with cardiovascular dysfunction, renal dysfunction and prolonged mechanical support.

Cost containment: the Americas. Argentina.

For many years, the evolution of Argentina's healthcare system has been influenced by political and economic instability. Inflation and hyperinflation have led to anarchic development of both health administration systems and hospitals. Critical care grew in a similar manner, resulting in a mix of > 500 critical care units with very different levels of technology and trained personnel. Cost-containment policies have been implemented mainly by health administration systems. Public institutions (university and large provincial and county hospitals) have suffered hard budget cuts that have resulted in a decrease in the quality of care and the loss of trained human resources. Union organizations, which cover the healthcare costs of > 60% of the population, implemented a low reimbursement policy that resulted in low standards of care for critically ill patients. The country's private hospital system is extremely heterogenous, ranging from little, simple institutions with a 20- to 30-bed capacity to great private institutions with international standards of care. Cost-containment efforts have been sporadic and isolated, and statistical data to analyze the results are lacking. In order to formulate a strategy of cost-containment in the near future, accreditation and categorization of critical care units and human resources training are being implemented by health authorities and the Argentine Society of Critical Care Medicine.

Lack of agreement between tonometric and gastric juice partial carbon dioxide tension.

STATEMENT OF FINDINGS: Our goal was to compare measurement of tonometered saline and gastric juice partial carbon dioxide tension (PCO2). In this prospective observational study, 112 pairs of measurements were simultaneously obtained under various hemodynamic conditions, in 15 critical care patients. Linear regression analysis showed a significant correlation between the two methods of measuring PCO2 (r(2) = 0.43; P < 0.0001). However, gastric juice PCO2 was systematically higher (mean difference 51 mmHg). The 95% limits of agreement were 315 mmHg and the dispersion increased as the values of PCO2 increased. Tonometric and gastric juice PCO2 cannot be used interchangeably. Gastric juice PCO2 measurement should be interpreted with caution.

Gastric mucosal pH as a prognostic index of mortality in critically ill patients.

OBJECTIVE: To determine if measurements of gastric intramucosal pH have prognostic implications regarding ICU mortality. DESIGN: Prospective comparison of outcome. SETTING: General adult ICUs in two teaching hospitals. PATIENTS: Eighty consecutive patients age 18 to 84 yrs (mean 63.4), 50 men and 30 women, 55% in the medical and 45% in the surgical services. METHODS: Gastric intramucosal pH was measured on ICU admission and again 12 hrs later. A value of greater than or equal to 7.35 was used to differentiate between normal and low gastric intramucosal pH. MEASUREMENTS AND MAIN RESULTS: Fifty-four patients had a normal gastric intramucosal pH and 26 patients had a low gastric intramucosal pH on ICU admission. The mortality rate was greater in the low gastric intramucosal pH group (65.4% vs. 43.6%; p less than .04). The frequency of sepsis and the presence of multisystem organ failure also were greater in the low gastric intramucosal pH group (p less than .01). Further stratification of patients according to gastric intramucosal pH measured 12 hrs after admission showed a greater mortality rate in patients with persistently low gastric intramucosal pH when compared with patients with normal gastric intramucosal pH during the first 12 hrs (86.7% vs. 26.8%; p less than .001). CONCLUSIONS: Measurements of gastric intramucosal pH on ICU admission, and again 12 hrs later, have a high specificity for predicting patient survival in this ICU patient population (77.8% to 80.6%). Furthermore, given its relative noninvasive nature, tonometrically measured gastric intramucosal pH may be a useful addition to patient monitoring in the ICU.

Gastric intramucosal pH as a therapeutic index of tissue oxygenation in critically ill patients.

Falls in gastric intramucosal pH (pHi) are associated with morbidity and mortality in patients admitted to intensive-care units (ICU). We tested the hypothesis that ICU outcome can be improved by therapy guided by changes in pHi and aimed at improving systemic oxygen availability. We studied 260 patients admitted to ICUs with APACHE II scores of 15-25. After insertion of a gastric tonometer, each patient was randomly assigned to a control or protocol group within the admission pHi category (normal = 7.35 or higher; low = below 7.35). The control groups were treated according to standard ICU practices. The protocol groups received, in addition, treatment to increase systemic oxygen transport or to reduce oxygen demand, whenever the pHi fell below 7.35 or by more than 0.10 units from the previous measurement. The protocol was used, because pHi fell, in 67 (85%) of the protocol group with normal pHi on admission. There were no significant differences between protocol and control groups in demographic characteristics, admission blood gases or haemoglobin concentration, number or type of organ system failures, or the intensity of ICU care. For patients admitted with low pHi, survival was similar in the protocol and control groups (37% vs 36%), whereas for those admitted with normal pHi, survival was significantly greater in the protocol than in the control group (58% vs 42%; p less than 0.01). Therapy guided by pHi measurements improved survival in patients whose pHi on admission to ICU was normal. pHi-guided resuscitation may help improve outcome in such patients by preventing splanchnic organ hypoxia and the development of a systemic oxygen deficit.

How is mechanical ventilation employed in the intensive care unit? An international utilization review.

A 1-d point-prevalence study was performed with the aim of describing the characteristics of conventional mechanical ventilation in intensive care units ICUs from North America, South America, Spain, and Portugal. The study involved 412 medical-surgical ICUs and 1,638 patients receiving mechanical ventilation at the moment of the study. The main outcome measures were characterization of the indications for initiation of mechanical ventilation, the artificial airways used to deliver mechanical ventilation, the ventilator modes and settings, and the methods of weaning. The median age of the study patients was 61 yr, and the median duration of mechanical ventilation at the time of the study was 7 d. Common indications for the initiation of mechanical ventilation included acute respiratory failure (66%), acute exacerbation of chronic obstructive pulmonary disease (13%), coma (10%), and neuromuscular disorders (10%). Mechanical ventilation was delivered via an endotracheal tube in 75% of patients, a tracheostomy in 24%, and a facial mask in 1%. Ventilator modes consisted of assist/control ventilation in 47% of patients and 46% were ventilated with synchronized intermittent mandatory ventilation, pressure support, or the combination of both. The median tidal volume setting was 9 ml/kg in patients receiving assist/control and the median setting of pressure support was 18 cm H(2)O. Positive end-expiratory pressure was not employed in 31% of patients. Method of weaning varied considerably from country to country, and even within a country several methods were in use. We conclude that the primary indications for mechanical ventilation and the ventilator settings were remarkably similar across countries, but the selection of modes of mechanical ventilation and methods of weaning varied considerably from country to country.

Early physiologic changes in canine fecal peritonitis.

Oxygen delivery (DO2) and related variables were studied in eight dogs during severe untreated peritonitis induced by cecal ligation and perforation. The development of peritonitis was accompanied by abdominal fluid sequestration and significant increases in hemoglobin (Hgb), arterial oxygen content (CaO2), and P50. Changes in mixed venous PO2 (P-vO2), mixed venous saturation (S-vO2), DO2, oxygen uptake (VO2), cardiac index (CI), and arteriovenous O2 difference (C[a--v]O2) were not significant. When blood volume was returned to normal levels with dextran, CI rose and C(a--v)O2 decreased; P-vO2 increased and Hgb returned to baseline levels. In this animal model, sepsis and fluid sequestration produced an increase in blood O2 capacity and CaO2, which sustained DO2 and VO2. No changes were observed in P-vO2 or S-vO2. The hyperdynamic state of severe sepsis became evident only after reversing hemoconcentration by colloid infusion. The increase in P-vO2 and S-vO2 after volume loading is possibly related to primary septic mechanisms and/or to changes in DO2.

Inmunoglobulina (ig) polivalente en el tratamiento de la sepsis abdominal / Polyvalent immunoglobulin (Ig) in the treatment of intraabdominal sepsis

La sepsis grave mantiene una elevada mortalidad en los últimos 40 años. Múltiples intentos por moderar la respuesta inflamatoria sistémica, mediante la infusión de inmunoglobulinas (Ig), han demostrado resultados controvertidos. Los diferentes criterios de diagnóstico, la diferente población en estudio y reducido número de pacientes, dificultan obtener conclusiones definitivas. Objetivo: Evaluar si la infusión de Ig mejora la evolución de pacientes con sepsis abdominal. Lugar: 7 unidades de Cuidados Intensivos Polivalentes. Diseño: Estudio multicéntrico, prospectivo, randomizado, doble ciego. Intervenciones: Los pacientes fueron asignados aleatoriamente para recibir Ig (Grupo A: GA) o placebo (Grupo B: GB) conjuntamente con el tratamiento habitual de la sepsis abdominal. Resultado: Treinta y siete pacientes fueron incluidos en el estudio. 20 en el GA y 17 en el GB. El nivel medio de APACHE II, TISS, las disfunciones y fallas orgánicas no fueron diferentes entre los grupos. La mortalidad general fue del 16,7 por ciento, superior en el GB (26 por ciento) respecto del GA (5 por ciento) aunque tal diferencia no alcanzó significación estadística. Conclusiones: Nuestros hallazgos sugieren, que la infusión de Ig (Pentaglobin) en pacientes con sepsis abdominal con foco resuelto, reduce la mortalidad al alta de la UCI. Nuevos estudios clínicos son necesarios para confirmar los presentes hallazgos

Respuesta hemodinamica y metabolica en la peritonitis en el perro. / Hemodynamic and metabolic response in peritonitis of dogs

Se estudiaron variables hemodinamicas y metabolicas en 9 perros antes y despues de la induccion de una peritonitis grave, y tras la expansion del volumen sanguineo.Los animales mantuvieron el VO2 en base a hemoconcentracion en la primera etapa y por aumento del VM en la segunda para compensar la lesion celular septica.Se discute el significado de ambas situaciones