Intralipid disappearance in critically ill patients

Intralipid elimination patterns were compared in 25 healthy controls, 12 patients recovering from uncomplicated cholecystectomy, and 25 critically ill patients. The intravenous fat tolerance test revealed a similar fractional removal rate (k2) in healthy controls and critically ill patients, but k2 was increased in cholecystectomy patients. The concentration of cross-reactive protein (CRP) correlated positively to the concentration of total triglyceride and low-density lipoprotein-triglyceride, and negatively to low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol. The extrapolated zero-time concentration of Intralipid in the critically ill patients was only one-third of the value in healthy controls. After this initial loss, however, Intralipid was removed from the circulation after first-order kinetics. These low concentrations of Intralipid were not correlated with concentrations of CRP. Possible explanations for this phenomenon include a change in the configuration of the lipid particles, the so-called creaming phenomenon, and/or immediate and substantial uptake of the emulsion by certain organs.     

Cardiopulmonary resuscitation in critically ill neurologic-neurosurgical patients

OBJECTIVES: To establish the rate of successful cardiopulmonary resuscitation (CPR) and to study outcome predictors in patients who experienced in-hospital cardiac arrest after being admitted to the neurologic-neurosurgical intensive care unit (ICU) with a primary neurologic diagnosis. PATIENTS AND METHODS: We identified patients admitted to the neurologic-neurosurgical ICU between 1994 and 2001 who experienced in-hospital cardiac arrest and received CPR. Functional outcome was assessed using the modified Rankin scale. RESULTS: During the study period, 38 consecutive patients experienced in-hospital cardiac arrest and received CPR. The median age of the patients was 65 years (range, 16-81 years), and the mean interval from admission to CPR was 12 days (range, 3 hours to 47 days). Acute intracranial disease was present in 32 patients (84%). Twenty-one patients (55%) were in the ICU at the time of the cardiac arrest; cardiac arrests in the wards occurred at a mean interval of 9 days (range, 1-45 days) after ICU discharge. Cardiopulmonary resuscitation achieved return of spontaneous circulation in 23 patients (61%). Seven patients (18%) were discharged from the hospital, 5 of whom later achieved a modified Rankin scale score of 2 or lower. Cardiac arrest after a deteriorating clinical course resulted in uniformly fatal outcomes. Duration of CPR shorter than 5 minutes and CPR in the ICU were associated with survival and good functional recovery. CONCLUSIONS: Cardiopulmonary resuscitation is a worthwhile procedure in severely ill neurologic-neurosurgical patients, regardless of the patient's age. However, the outcome after CPR appears much worse in patients with a prior deteriorating clinical course.     

Propofol infusion syndrome in critically ill patients

OBJECTIVE: To describe the clinical presentation of propofol infusion syndrome in critically ill adults. DATA SOURCES: Clinical literature was accessed through MEDLINE (1966 - March 2001). Key search terms included Diprivan, propofol, and propofol infusion syndrome. Case reports and small case series evaluating the use and toxicity of propofol in sedating critically ill adults were reviewed. DATA SYNTHESIS: The association between propofol infusion syndrome and death in children secondary to myocardial failure is well documented. However, few data are available regarding the syndrome in critically ill adults. Based on a review of those data, it appears that propofol infusion syndrome can occur in both children and adults. Common clinical features of propofol infusion syndrome may include hyperkalemia, hepatomegaly, lipemia, metabolic acidosis, myocardial failure, and rhabdomyolysis. Although the premise has not been proven, recent published cases appear to demonstrate an association between propofol infusion and death secondary to myocardial failure. CONCLUSIONS: Until further safety data become available, caution should be exercised when using high-dose (>5 mg/kg/h) and long-term (>48 h) propofol infusion in sedating critically ill adults.     

An insulin infusion protocol in critically ill cardiothoracic surgery patients

BACKGROUND: Critically ill cardiothoracic patients are prone to hyperglycemia and an increased risk of surgical site infections postoperatively. Aggressive insulin treatment is required to achieve tight glycemic control (TGC) and improve outcomes. OBJECTIVE: To examine and report on the performance of an insulin infusion protocol to maintain TGC, defined as a blood glucose level of 80-150 mg/dL, in critically ill cardiothoracic surgical patients. METHODS: A nurse-driven insulin infusion protocol was developed and initiated in postoperative cardiothoracic surgical intensive care patients with or without diabetes. In this before-after cohort study, 2 periods of measurement were performed: a 6-month baseline period prior to the initiation of the insulin infusion protocol (control group, n = 174) followed by a 6-month intervention period in which the protocol was used (TGC group, n = 168). RESULTS: Findings showed percent and time of blood glucose measurements within the TGC range (control 47% vs TGC 61%; p = 0.001), AUC of glucose exposure >150 mg/dL versus time for the first 24 hours of the insulin infusion (control 28.4 vs TGC 14.8; p < 0.001), median time to blood glucose <150 mg/dL (control 9.4 h vs TGC 2.1 h; p < 0.001), and percent blood glucose <65 mg/dL as a marker for hypoglycemia (control 9.8% vs TGC 16.7%; NS). CONCLUSIONS: An insulin infusion protocol designed to achieve a goal blood glucose range of 80-150 mg/dL efficiently and significantly improved TGC in critically ill postoperative cardiothoracic surgery patients without significantly increasing the incidence of hypoglycemia.     

Pharmacokinetics of prolonged infusion of high-dose dexmedetomidine in critically ill patients

Introduction

Only limited information exists on the pharmacokinetics of prolonged (> 24 hours) and high-dose dexmedetomidine infusions in critically ill patients. The aim of this study was to characterize the pharmacokinetics of long dexmedetomidine infusions and to assess the dose linearity of high doses. Additionally, we wanted to quantify for the first time in humans the concentrations of H-3, a practically inactive metabolite of dexmedetomidine.

Methods

Thirteen intensive care patients with mean age of 57 years and Simplified Acute Physiology Score (SAPS) II score of 45 were included in the study. Dexmedetomidine infusion was commenced by using a constant infusion rate for the first 12 hours. After the first 12 hours, the infusion rate of dexmedetomidine was titrated between 0.1 and 2.5 μg/kg/h by using predefined dose levels to maintain sedation in the range of 0 to -3 on the Richmond Agitation-Sedation Scale. Dexmedetomidine was continued as long as required to a maximum of 14 days. Plasma dexmedetomidine and H-3 metabolite concentrations were measured, and pharmacokinetic variables were calculated with standard noncompartmental methods. Safety and tolerability were assessed by adverse events, cardiovascular signs, and laboratory tests.

Results

The following geometric mean values (coefficient of variation) were calculated: length of infusion, 92 hours (117%); dexmedetomidine clearance, 39.7 L/h (41%); elimination half-life, 3.7 hours (38%); and volume of distribution during the elimination phase, 223 L (35%). Altogether, 116 steady-state concentrations were found in 12 subjects. The geometric mean value for clearance at steady state was 53.1 L/h (55%). A statistically significant linear relation (r ² = 0.95; P < 0.001) was found between the areas under the dexmedetomidine plasma concentration-time curves and cumulative doses of dexmedetomidine. The elimination half-life of H-3 was 9.1 hours (37%). The ratio of AUC_0-∞ of H-3 metabolite to that of dexmedetomidine was 1.47 (105%), ranging from 0.29 to 4.4. The ratio was not statistically significantly related to the total dose of dexmedetomidine or the duration of the infusion.

Conclusions

The results suggest linear pharmacokinetics of dexmedetomidine up to the dose of 2.5 μg/kg/h. Despite the high dose and prolonged infusions, safety findings were as expected for dexmedetomidine and the patient population.

Trial Registration

ClinicalTrials.gov: NCT00747721     

Cardiopulmonary assessment of the critically ill trauma patient

The adequacy of tissue oxygenation status of trauma patients requires close surveillance of cardiopulmonary functioning. A thorough assessment includes the parameters that evaluate pulmonary gas exchange, oxygen delivery to the tissues, and oxygen utilization by the tissues.     

Short-term amino acid infusion improves protein balance in critically ill patients

IntroductionEvidence behind the recommendations for protein feeding during critical illness is weak. Mechanistic studies are needed to elucidate the effects of amino acid and/or protein supplementation on protein metabolism before larger clinical trials with higher levels of protein feeding are initiated.MethodsWe studied the effects of parenteral amino acid supplementation (equivalent to 1 g/kg/day) over the course of 3 hours on whole-body protein turnover in critically ill patients in the intensive care unit (ICU) during the first week after admission. Patients were studied at baseline during ongoing nutrition and during extra amino acid supplementation. If the patient was still in the ICU 2 to 4 days later, these measurements were repeated. Protein kinetics were measured using continuous stable isotope-labeled phenylalanine and tyrosine infusions.ResultsThirteen patients were studied on the first study occasion only, and seven were studied twice. Parenteral amino acid supplementation significantly improved protein balance on both occasions, from a median of −4 to +7 μmol phenylalanine/kg/hr (P =0.001) on the first study day and from a median of 0 to +12 μmol phenylalanine/kg/hr (P =0.018) on the second study day. The more positive protein balance was attributed to an increased protein synthesis rate, which reached statistical significance during the first measurement (from 58 to 65 μmol phenylalanine/kg/hr; n =13; P =0.007), but not during the second measurement (from 58 to 69 μmol phenylalanine/kg/hr; n =7; P =0.09). Amino acid oxidation rates, estimated by phenylalanine hydroxylation, did not increase during the 3-hour amino acid infusion. A positive correlation (r =0.80; P <0.0001) was observed between total amino acids and/or protein given to the patient and whole-body protein balance.ConclusionExtra parenteral amino acids infused over a 3-hour period improved whole-body protein balance and did not increase amino acid oxidation rates in critically ill patients during the early phase (first week) of critical illness.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-015-0844-6) contains supplementary material, which is available to authorized users.     

Efficacy and safety of potassium infusion therapy in hypokalemic critically ill patients

OBJECTIVE: To evaluate the efficacy and safety of potassium replacement infusions in critically ill patients. DESIGN: Prospective cohort study. SETTING: Multidisciplinary critical care unit. PATIENTS: Forty-eight critically ill adult patients, age 25 to 86 yrs. Patients entered the study when hypokalemia (potassium less than 3.5 mmol/L) was noted on routine laboratory blood analysis. Most common primary diagnoses on ICU admission included postoperative cardiac surgery (n = 9), sepsis and multiple organ system failure (n = 9), complicated myocardial infarction (n = 7), and respiratory failure (n = 5). INTERVENTION: Potassium chloride infusions (20, 30, or 40 mmol in 100 mL normal saline over 1 hr) were administered to patients for serum potassium levels of less than 3.5 but greater than 3.2 mmol/L (n = 26), 3.0 to 3.2 mmol/L (n = 11), and less than 3.0 mmol/L (n = 11), respectively. Serum and urine potassium levels were monitored during and for 1 hr after the infusion. MEASUREMENTS AND RESULTS: All patients tolerated the infusions without evidence of hemodynamic compromise, ECG change, or new dysrhythmia requiring treatment. The mean maximum potassium increase was 0.5 +/- 0.3 mmol/L, 0.9 +/- 0.4 mmol/L, and 1.1 +/- 0.4 mmol/L in the 20-, 30-, and 40-mmol groups, respectively. The increase in serum potassium was maximal at the completion of the infusion and was significant (p less than .05) compared with baseline in all groups. Peak potassium levels were the same in patients with normal renal function (n = 33) compared with those with renal insufficiency (n = 15). Urinary excretion of potassium increased in all groups during the infusion and was significant (p less than .05) in the 30- and 40-mmol groups, but was no greater in those patients who had received diuretics (n = 8) compared with those patients who had not (n = 40). CONCLUSIONS: In the select group of hypokalemic patients studied, potassium infusions of 20 to 40 mmol delivered over 1 hr were safe to administer and effectively increased serum potassium levels in a dose-dependent and predictable fashion. Furthermore, these results were independent of the patient's underlying renal function or associated diuretic administration.     

Continuous infusion versus intermittent administration of meropenem in critically ill patients.

This prospective crossover study compared the pharmacokinetics of meropenem by continuous infusion and by intermittent administration in critically ill patients. Fifteen patients were randomized to receive meropenem either as a 2 g iv loading dose, followed by a 3 g continuous infusion (CI) over 24 h, or by intermittent administration (IA) of 2 g iv every 8 h (q8h). Each regimen was followed for a period of 2 days, succeeded by crossover to the alternative regimen for the same period. Pharmacokinetic parameters (mean +/- SD) of CI included the following: concentration at steady state (Css) was 11.9+/-5.0 mg/L; area under the curve (AUC) was 117.5+/-12.9 mg/L x h. The maximum and minimum serum concentrations of meropenem (Cmax, Cmin) and total meropenem clearance (CItot) for IA were 110.1+/-6.9 mg/L, 8.5+/-1.0 mg/L and 9.4+/-1.2 L/h, respectively. The AUC during the IA regimen was larger than the AUC during CI (P < 0.001). In both treatment groups, meropenem serum concentrations remained above the MICs for the most common bacterial pathogens. We conclude that CI of meropenem is equivalent to the IA regimen and is therefore suitable for treating critically ill patients. Further studies are necessary to compare the clinical effects of CI and IA in this patient group.     

Albumin bolus administration versus continuous infusion in critically ill hypoalbuminemic pediatric patients

Objective To test the hypothesis that the rate of degradation of exogenously administered albumin is fater with bolus administration that with continuous infusion and thus that a bolus administration is less efficacious in restoring blood albumin concentration (BAC) in the hypoalbuminemic critically ill pediatric patient.Design A prospective, controlled study of two groups of patients.Setting Pediatric intensive care unit (PICU) of a children's hospital.Patients 37 cirtically ill hypoalbuminemic patients. (BAC2.8 g/dl), in whom no overt protein-losing disease was identified, were divided into two treatment groups and included in a 60-h study.Interventions 18 patients were given an i.v. bolus of 1 g/kg of 25% albumin over 4 h. This treatment was repeated after 24 and 48 h. Nineteen other patients were given the same dose of 1 g/kg of 25% albumin as a continuous 24-h infusion throughout the 60-h study period. BAC along with sodium, potassium, and total and ionized calcium were measured in the serum of blood samples obtained at predetermined intervals.Measurement and main results A 4 h bolus of albumin resulted in an acute rise in BAC, which declined to baseline within 24 h. A continuous infusion resulted in a steady rise in BAC with 24-h levels significantly higher than baseline. The percent change in mean BAC from baseline, calculated at 12-h intervals during the 60-h study period, showed a steady increase in the continuous infusion group with a 34% increase after the first 24 h. In contrast, the 4-h bolus method resulted in major fluctuations in the BAC values with only a 14% increase (p<0.05) after 24 h. Albumin's volume of distribution, half-life and elimination constant, calculated based on blood albumin values during the first 24 h after the bolus administration, were 0.12±0.03 1/kg, 4.6±1.8 h and 0.17±0.06 h^–1, respectively. This half-life did not apply to the continuous infusion group as a steady state was not achieved after 30 h (6 half-lives), and BAC continued to rise throughout the 60-h study period. No significant changes in blood electrolytes were observed with either method.Conclusions The half-life of exogenous albumin in the critically ill hypoalbuminemic pediatric patient is short if given as a bolus. Continuous infusion therapy appears to be more efficacious in increasing BAC over time, as the half-life with this method appears to be longer.An abstract of this paper was presented at the SCCM meeting in Orlando, Florida in February 1994.     

The haemodynamic effects of intermittent haemofiltration in critically ill patients

The haemodynamic effects of intermittent high volume venovenous haemofiltration were studied in 13 critically ill patients. The mean negative fluid balance during filtration was 1.2l and the mean duration of treatment 3 h 40 min. The cardiac index fell initially (4.5±0.2 to 3.8±0.2l/min/m²;p<0.05) but then remained stable throughout treatment before returning to baseline at the end of haemofiltration. The mean arterial pressure was unchanged with an increase in the systemic vascular resistance (651±33 to 765±65 dyne·s/cm⁵;p<0.05) suggesting that vascular responsiveness is maintained during haemofiltration.     

Hyponatremia in critically ill patients

Disorders of sodium and water metabolism are frequently encountered in hospitalized patients. Hyponatremia in critically ill patients can cause significant morbidity and mortality. Inappropriate treatment of hyponatremia can add to the problem. The diagnosis and management of salt and water abnormalities in critically ill patients is often challenging. The increasing knowledge about aquaporins and the role of vasopressin in water metabolism has enhanced our understanding of these disorders. The authors have outlined the general approach to the diagnosis and management of hyponatremia. A systematic approach by clinicians, using a detailed history, physical examination, and relevant diagnostic tests, will assist in efficient management of salt and water problems.     

Delirium in critically ill patients

Delirium in the intensive care unit is a serious problem that has recently attracted much attention. User-friendly and reliable tools, such as the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), offer the clinician the opportunity to identify delirium in patients better. Diagnosis of delirium in a critical care population is often a difficult task because classical psychiatric evaluation is impossible for a number of reasons. The CAM-ICU makes use of nonverbal assessments to evaluate the cardinal features of delirium (i.e. acute or fluctuating onset, inattention, disorganized thinking and altered level of consciousness). Its development for use in the critical care setting represents a significant advance that could lead to better care for such patients.     

Myopathy in critically ill patients

OBJECTIVE: To review myopathic changes occurring during intensive care treatment in the light of recent information about manifestation, clinical settings, pathophysiology, and histomorphologic changes. DATA SOURCES: The computerized MEDLINE database, bibliography of pertinent articles, and the author's personal files. STUDY SELECTION: Studies were selected according to their relevance to myopathic complications in critically ill patients. DATA EXTRACTION: All applicable data were extracted. DATA SYNTHESIS: Myopathic changes occur frequently in patients treated in the intensive care unit (ICU). Three main types have been identified: critical illness myopathy, myopathy with selective loss of myosin filaments, and acute necrotizing myopathy of intensive care. These histologic types probably represent variable expressions of a toxic effect not yet identified. Candidates for such myotoxic effects are the mediators of the systemic response in sepsis and high-dose administration of corticosteroids and muscle relaxants. The influence of these latter agents appears to be particularly important in the pathogenesis of myosin loss and myonecrosis. Experimental studies suggest that axonal damage attributable to critical illness neuropathy can be an additional factor triggering myopathies in the ICU. Muscle membrane inexcitability was recently identified as an alternative mechanism of severe weakness in ICU patients. CONCLUSIONS: Myopathic changes are surprisingly frequent in critically ill patients. The clinical importance of this finding is still unknown, but it is likely that weakness caused by myopathy prolongs ICU stay and rehabilitation. Because corticosteroids and muscle relaxants appear to trigger some types of ICU myopathy, they should be avoided or administered at the lowest doses possible. Sepsis, denervation, and muscle membrane inexcitability may be additional factors. Studies addressing the pathophysiology of myopathy in critically ill patients are urgently needed.     

Hypernatremia in critically ill patients

Hypernatremia is common in intensive care units. It has detrimental effects on various physiologic functions and was shown to be an independent risk factor for increased mortality in critically ill patients. Mechanisms of hypernatremia include sodium gain and/or loss of free water and can be discriminated by clinical assessment and urine electrolyte analysis. Because many critically ill patients have impaired levels of consciousness, their water balance can no longer be regulated by thirst and water uptake but is managed by the physician. Therefore, the intensivists should be very careful to provide the adequate sodium and water balance for them. Hypernatremia is treated by the administration of free water and/or diuretics, which promote renal excretion of sodium. The rate of correction is critical and must be adjusted to the rapidity of the development of hypernatremia.