Rik T. Gerritsen

Effects of nitroglycerin on sublingual microcirculatory blood flow in patients with severe sepsis/septic shock after a strict resuscitation protocol: a double-blind randomized placebo controlled trial.

Objectives:Microcirculatory alterations have been associated with morbidity and mortality in human sepsis. Such alterations occur despite pressure-guided resuscitation. Earlier data suggested that impaired microcirculatory blood flow could be corrected with intravenous nitroglycerin in these patients. We tested this concept after fulfillment of preset systemic hemodynamic resuscitation end points in the early phase of sepsis. Design:Prospective, single center, randomized, placebo-controlled, double-blind clinical trial. Setting:Closed-format 22-bed mixed intensive care unit in a tertiary teaching hospital. Patients:Patients ≥18 yrs with sepsis, according to international criteria, and at least one early sign of organ dysfunction, as the principal reason for intensive care unit admission, were eligible for enrollment. Interventions:Patients were randomly assigned to receive nitroglycerin (n = 35) or placebo (n = 35) after fulfillment of protocol-driven resuscitation end points. This trial is registered with ClinicalTrials.gov as NCT00493415. Measurements and Main Results:Primary outcome was sublingual microcirculatory blood flow of small vessels, as assessed by side-stream dark field imaging. After protocolized resuscitation, we observed recruitment of sublingual microcirculation in both groups, as indicated by a significant improvement in the microcirculatory flow index after 24 hrs, in comparison to baseline. However, no difference in the sublingual microvascular flow index was observed between groups. The median microvascular flow index in sublingual small-sized vessels was 2.71 (1.85-3) in the nitroglycerin group and 2.71 (1.27-3), p = .80, in the placebo group. In medium-sized vessels, the respective values were 3 (2.75-3) vs. 2.86 (2.19-3), p = .21, and in large-sized vessels, 3 (3-3) vs. 3 (2.89-3), p = .06. In-hospital mortality, as a secondary outcome, was 34.3% in the nitroglycerin group and 14.2% in the placebo group, p = .09. Conclusions:In the context of a strict resuscitation protocol, based upon fulfillment of systemic hemodynamic end points in patients with early-phase severe sepsis or septic shock, we conclude that intravenous nitroglycerin does not promote sublingual microcirculatory blood flow.

Guidelines for Family-Centered Care in the Neonatal, Pediatric, and Adult ICU.

Objective: To provide clinicians with evidence-based strategies to optimize the support of the family of critically ill patients in the ICU. Methods: We used the Council of Medical Specialty Societies principles for the development of clinical guidelines as the framework for guideline development. We assembled an international multidisciplinary team of 29 members with expertise in guideline development, evidence analysis, and family-centered care to revise the 2007 Clinical Practice Guidelines for support of the family in the patient-centered ICU. We conducted a scoping review of qualitative research that explored family-centered care in the ICU. Thematic analyses were conducted to support Population, Intervention, Comparison, Outcome question development. Patients and families validated the importance of interventions and outcomes. We then conducted a systematic review using the Grading of Recommendations, Assessment, Development and Evaluations methodology to make recommendations for practice. Recommendations were subjected to electronic voting with pre-established voting thresholds. No industry funding was associated with the guideline development. Results: The scoping review yielded 683 qualitative studies; 228 were used for thematic analysis and Population, Intervention, Comparison, Outcome question development. The systematic review search yielded 4,158 reports after deduplication and 76 additional studies were added from alerts and hand searches; 238 studies met inclusion criteria. We made 23 recommendations from moderate, low, and very low level of evidence on the topics of: communication with family members, family presence, family support, consultations and ICU team members, and operational and environmental issues. We provide recommendations for future research and work-tools to support translation of the recommendations into practice. Conclusions: These guidelines identify the evidence base for best practices for family-centered care in the ICU. All recommendations were weak, highlighting the relative nascency of this field of research and the importance of future research to identify the most effective interventions to improve this important aspect of ICU care.

Determinants of Procedural Pain Intensity in the Intensive Care Unit. The Europain® Study

RATIONALE Intensive care unit (ICU) patients undergo several diagnostic and therapeutic procedures every day. The prevalence, intensity, and risk factors of pain related to these procedures are not well known. OBJECTIVES To assess self-reported procedural pain intensity versus baseline pain, examine pain intensity differences across procedures, and identify risk factors for procedural pain intensity. METHODS Prospective, cross-sectional, multicenter, multinational study of pain intensity associated with 12 procedures. Data were obtained from 3,851 patients who underwent 4,812 procedures in 192 ICUs in 28 countries. MEASUREMENTS AND MAIN RESULTS Pain intensity on a 0-10 numeric rating scale increased significantly from baseline pain during all procedures (P < 0.001). Chest tube removal, wound drain removal, and arterial line insertion were the three most painful procedures, with median pain scores of 5 (3-7), 4.5 (2-7), and 4 (2-6), respectively. By multivariate analysis, risk factors independently associated with greater procedural pain intensity were the specific procedure; opioid administration specifically for the procedure; preprocedural pain intensity; preprocedural pain distress; intensity of the worst pain on the same day, before the procedure; and procedure not performed by a nurse. A significant ICU effect was observed, with no visible effect of country because of its absorption by the ICU effect. Some of the risk factors became nonsignificant when each procedure was examined separately. CONCLUSIONS Knowledge of risk factors for greater procedural pain intensity identified in this study may help clinicians select interventions that are needed to minimize procedural pain. Clinical trial registered with www.clinicaltrials.gov (NCT 01070082).

Furosemide does not improve renal recovery after hemofiltration for acute renal failure in critically ill patients: a double blind randomized controlled trial.

Objective:To study the potential beneficial role of furosemide in resolving renal failure after hemofiltration in mechanically ventilated critically ill patients. Design:Single-center randomized, double blind, placebo-controlled study. Setting:A 13-bed mixed intensive care unit (ICU) in a teaching hospital. Patients:Patients who had been treated with continuous venovenous hemofiltration were included. Interventions:After the end of continuous venovenous hemofiltration, the urine of the first 4 hours was collected for measuring creatinine clearance. Patients were subsequently randomized for furosemide (0.5 mg/kg/hr) or placebo by continuous infusion. To prevent hypovolemia, the rate of fluid infusion was adapted every hour and was set as the urinary production of the previous hour. Measurements and Main Results:End points were renal recovery (creatinine clearance more than 30 mL/min or stable serum creatinine without renal replacement therapy) in the ICU and in the hospital. Seventy-two patients were included and 71 were eligible for the analysis. The 36 furosemide-treated patients had a significantly increased urinary volume compared with the 35 placebo-treated patients (median 247 mL/hr (interquartile range [IQR] 774 mL/hr) vs. 117 mL/hr (IQR 158 mL/hr), p = 0.003) and greater sodium excretion (median 73 mmol/L (IQR 48) vs. 37 (IQR 48) mmol/L, p = 0.001). In the furosemide group 25 patients and in the placebo group 27 patients showed recovery of renal function at ICU discharge (p = 0.46). Two patients of the furosemide group needed long-term dialysis dependency (p = 0.23). Conclusion:Furosemide by continuous infusion in the recovery phase of hemofiltration-dependent acute kidney failure did increase urinary volume and sodium excretion but did not lead to a shorter duration of renal failure or more frequent renal recovery.

Albumin-adjusted calcium is not suitable for diagnosis of hyper- and hypocalcemia in the critically ill.

ObjectiveTo evaluate whether calcium adjusted for albumin can be used to monitor calcium homeostasis in critically ill patients. DesignProspective single-single center observational study. SettingClinical laboratory and critical care unit of a regional teaching hospital. PatientsFifty-three paired samples were from 36 patients requiring intensive care treatment. InterventionsNone. Measurements and Main ResultsTotal calcium, albumin-adjusted calcium, and ionized calcium were measured in critically ill patients during an 8-wk period. Calcium was adjusted for albumin using the formula that is most frequently used in The Netherlands. Using ionized calcium as the gold standard, albumin-adjusted calcium overestimated hypercalcemia and totally missed hypocalcemia. The same seemed to be true for other formulas used for albumin or protein adjustment of calcium concentrations. ConclusionsAlbumin-adjusted calcium cannot be used in an intensive care setting to monitor reliably the calcium levels in critically ill patients and should be replaced by measurement of ionized calcium.

HDL-cholesterol level and cortisol response to synacthen in critically ill patients

ObjectiveTo explore the relationship between cholesterol levels and the adrenal cortisol response to synacthen in critically ill patients.DesignProspective observational study.PatientsCritically ill patients with multiple organ dysfunction syndrome (MODS) with possible adrenal dysfunction defined as unexplained hypotension, ongoing inotropic support, unexplained fever, unexplained hyponatraemia or a combination of these symptoms.MeasurementsHDL-cholesterol levels (HDL), total cholesterol levels (TC), and triglycerides (TG) before administration of synacthen. LDL-cholesterol was calculated using the Friedewald formula. Basal cortisol and response to 250 μg synacthen intravenously was measured. A cortisol rise of 0.25 μmol/l in a 30-min or 60-min blood sample after synacthen infusion was defined as a proper adrenal response.ResultsPatients with a proper response to synacthen showed higher HDL-cholesterol levels than patients without that response (P=0.02). Severity of disease as measured by APACHE II or SOFA was not a confounder. LDL-cholesterol levels were extremely low in both responders and non-responders and were not associated with the absolute rise in cortisol. In linear and logistic regression analysis HDL-cholesterol was the sole predictor of cortisol response.ConclusionsAdrenal cortisol response to a “classic” 250-μg synacthen test relates in critically ill patients to HDL-cholesterol levels. LDL and TC levels did not show such a relation. These findings are in concordance with known biochemical pathways of cortisol production.

Filter Run Time in CVVH: Pre- versus Post-Dilution and Nadroparin versus Regional Heparin-Protamine Anticoagulation

Background/Aims: To study the effect of different modes of continuous veno-venous haemofiltration (CVVH) on filter run time (FRT). Methods: We studied, in two consecutive prospective, randomised and crossover studies, 16 and 15 patients with acute renal failure during critical illness. Study A compared pre- versus post-dilution, and study B compared regional anticoagulation with heparin (pre-filter) and protamine (post-filter) (HP) versus nadroparin (NP) pre-filter. All CVVH sessions were standardised. Analyses were by Wilcoxon rank sum tests. Results: Study A: During pre-dilution the median FRT was 45.7 vs. 16.1 h in post-dilution CVVH (p = 0.005). The median creatinine clearance during pre-dilution was 33 vs. 45 ml/min in post-dilution (p = 0.001). Study B: During NP, median FRT was 39.5 vs. 12.3 h during HP CVVH (p = 0.045). Conclusions: Pre-dilution CVVH results in the greatest FRT but a lower plasma creatinine clearance compared to post-dilution. Regional anticoagulation with heparin-protamine resulted in a significantly shorter FRT compared to systemic NP anticoagulation.

Perception by Family Members and ICU Staff of the Quality of Dying and Death in the ICU: A Prospective Multicenter Study in The Netherlands

OBJECTIVE Admission to the ICU is a major event in a patient’s life and also for family members. We tried to elucidate how family members and ICU caregivers experience the dying process of their patients. METHODS The prospective study took place in three Dutch ICUs. Patients who had stayed . 48 h and died in the ICU were eligible. The Quality of Dying and Death (QODD) questionnaire was used, with addition of items pertaining to the patient’s autonomy. Values indicate median and interquartile range. RESULTS We included 100 consecutive patients. ICU stay before death was 8 (3-16) days. APACHE (Acute Physiology and Chronic Health Evaluation) II score at admission was 24 (19-31). Family response rate was 89%. Families were satisfied with overall QODD (score, 8 [7-9]) and felt supported by the ICU caregivers (8 [7-9]). Pain control was scored lower by family members (8 [5.75- 8.25]) than by nurses and physicians (9 [8-10], P 5 .024) Almost always, physicians discussed the patient’s end-of-life wishes with family members, although families rated the quality of the discussion lower (7 [5.5-8.5]) than physicians (9 [6.5-10]) ( P 5 .045). The majority of the families (89%) felt included in the decision-making process. More than one-half of the family members (57%) believed that the physician made the fi nal decision alone after giving information, whereas 36.8% believed they had participated in making the decision. Family members rated the QODD questionnaire as difficult (6 [5-8]), and several items were not answered by a majority of family members. CONCLUSIONS Quality of dying and death is generally perceived to be good by family members and caregivers of patients who die in Dutch ICUs. There is a need for modification of the QODD questionnaire for the European ICU population.

Comparing Quality of Dying and Death Perceived by Family Members and Nurses for Patients Dying in US and Dutch ICUs

Background: The Quality of Dying and Death (QODD) questionnaire is used as a self‐reported measure to allow families and clinicians to assess patients’ quality of dying and death. We evaluated end‐of‐life (EOL) experiences as measured by the QODD completed by families and nurses in the United States and the Netherlands to explore similarities and differences in these experiences and identify opportunities for improving EOL care. Methods: Questionnaire data were gathered from family members of patients dying in the ICU and nurses caring for these patients. In The Netherlands, data were gathered in three teaching hospitals, and data was gathered from 12 sites participating in a randomized trial in the United States. The QODD consists of 25 items and has been validated in the United States. Results: Data from 446 patients were analyzed (346 in the United States and 100 in the Netherlands). Dutch patients were older than those in the United States (72 + 10.2 years vs 65 + 16.0 years; P < .0025). The family‐assessed overall QODD score was the same in both countries: the Netherlands = median, 9; interquartile range (IQR), 8–10 and the United States = median, 8; IQR, 5–10. US family members rated the quality of two items higher than did the Netherlands families: “time spent with loved ones” and “time spent alone.” Nurse‐assessed QODD ratings varied: the single‐item QODD summary score was significantly higher in the Netherlands (the Netherlands: median, 9; IQR, 8–10 vs the United States: median, 7; IQR, 5–8; P < .0025), whereas the QODD total score was higher in the United States (the Netherlands: median, 6.9; IQR, 5.5–7.6 vs the United States: median, 7.1; IQR, 5.8–8.4; P = .014), although it did not meet our criteria for statistical significance. Of the 22 nurse‐assessed items, 10 were significantly different between the Netherlands and the United States, with eight having higher scores in the United States and 2 having higher scores in the Netherlands. Conclusions: The QODD was rated similarly by family members in the United States and the Netherlands but varied when assessed by nurses. These differences may be due to organizational or cultural differences between the two countries or to expectations of respondents.

Pain distress: the negative emotion associated with procedures in ICU patients

PurposeThe intensity of procedural pain in intensive care unit (ICU) patients is well documented. However, little is known about procedural pain distress, the psychological response to pain.MethodsPost hoc analysis of a multicenter, multinational study of procedural pain. Pain distress was measured before and during procedures (0–10 numeric rating scale). Factors that influenced procedural pain distress were identified by multivariable analyses using a hierarchical model with ICU and country as random effects.ResultsA total of 4812 procedures were recorded (3851 patients, 192 ICUs, 28 countries). Pain distress scores were highest for endotracheal suctioning (ETS) and tracheal suctioning, chest tube removal (CTR), and wound drain removal (median [IQRs] = 4 [1.6, 1.7]). Significant relative risks (RR) for a higher degree of pain distress included certain procedures: turning (RR = 1.18), ETS (RR = 1.45), tracheal suctioning (RR = 1.38), CTR (RR = 1.39), wound drain removal (RR = 1.56), and arterial line insertion (RR = 1.41); certain pain behaviors (RR = 1.19–1.28); pre-procedural pain intensity (RR = 1.15); and use of opioids (RR = 1.15–1.22). Patient-related variables that significantly increased the odds of patients having higher procedural pain distress than pain intensity were pre-procedural pain intensity (odds ratio [OR] = 1.05); pre-hospital anxiety (OR = 1.76); receiving pethidine/meperidine (OR = 4.11); or receiving haloperidol (OR = 1.77) prior to the procedure.ConclusionsProcedural pain has both sensory and emotional dimensions. We found that, although procedural pain intensity (the sensory dimension) and distress (the emotional dimension) may closely covary, there are certain factors than can preferentially influence each of the dimensions. Clinicians are encouraged to appreciate the multidimensionality of pain when they perform procedures and use this knowledge to minimize the patient’s pain experience.