Metabolic effects of intensive insulin therapy in critically ill patients.

Our aim was to investigate the effects of glycemic control and insulin concentration on lipolysis, glucose, and protein metabolism in critically ill medical patients. For our methods, the patients were studied twice. In study 1, blood glucose (BG) concentrations were maintained between 7 and 9 mmol/l with intravenous insulin. After study 1, patients entered one of four protocols for 48 h until study 2: low-insulin high-glucose (LIHG; variable insulin, BG of 7-9 mmol/l), low-insulin low-glucose (LILG; variable insulin of BG 4-6 mmol/l), high-insulin high-glucose [HIHG; insulin (2.0 mU . kg(-1).min(-1) plus insulin requirement from study 1), BG of 7-9 mmol/l], or high-insulin low-glucose [HILG; insulin (2.0 mU.kg(-1).min(-1) plus insulin requirement from study 1), BG of 4-6 mmol/l]. Age-matched healthy control subjects received two-step euglycemic hyperinsulinemic clamps achieving insulin levels similar to the LI and HI groups. In our results, whole body proteolysis was higher in patients in study 1 (P < 0.006) compared with control subjects at comparable insulin concentrations and was reduced with LI (P < 0.01) and HI (P = 0.001) in control subjects but not in patients. Endogenous glucose production rate (R(a)), glucose disposal, and lipolysis were not different in all patients in study 1 compared with control subjects at comparable insulin concentrations. Glucose R(a) and lipolysis did not change in any of the study 2 patient groups. HI increased glucose disposal in the patients (HIHG, P = 0.001; HILG, P = 0.07 vs. study 1), but this was less than in controls receiving HI (P < 0.03). In conclusion, low-dose intravenous insulin administered to maintain BG between 7-9 mmol/l is sufficient to limit lipolysis and endogenous glucose R(a) and increase glucose R(d). Neither hyperinsulinemia nor normoglycemia had any protein-sparing effect.

Factors influencing the effectiveness of endovenous laser ablation (EVLA) in the treatment of great saphenous vein reflux.

OBJECTIVE: Endovenous laser ablation (EVLA) is an alternative to surgery for treating sapheno-femoral and great saphenous vein (GSV) reflux. This study assesses factors that might influence its effectiveness. DESIGN: Prospective, observational study. METHOD: EVLA was used to treat the great saphenous vein in 644 limbs as part of the management of varicose veins. Body mass index (BMI), maximum GSV diameter, length of vein treated, total laser energy (TLE) and energy density (ED: Joules/cm) delivered were recorded prospectively. Data from limbs with ultrasound confirmed GSV occlusion at 3-months were compared with those where the GSV was partially occluded or patent. Complications were recorded prospectively. RESULTS: GSV occlusion was achieved in 599/644 (93%) limbs (group A). In 45 limbs (group B) the vein was partially occluded (n=19) or patent (n=26). Neither BMI [group A: 25.2 (23.0-28.5); group B: 25.1 (24.3-26.2)], nor GSV diameter [A: 7.2mm (5.6-9.2); B: 6.9 mm (5.5-7.7)] influenced success. TLE and ED were greater p<0.01) in group A (median [inter-quartile range]: 1877J (997-2350), 48 (37-59)J/cm) compared to group B (1191J (1032-1406), 37 (30-46)J/cm). Although TLE reflects the greater length of GSV ablated in Group A (33 cm v 29 cm, p=0.06) this does not influence ED. GSV occlusion always occurred when ED>/=60 J/cm with no increase in complications. CONCLUSIONS: ED (J/cm) of laser delivery is the main determinant of successful GSV ablation following EVLA.

Nerve excitability changes in critical illness polyneuropathy.

Patients in intensive care units frequently suffer muscle weakness and atrophy due to critical illness polyneuropathy (CIP), an axonal neuropathy associated with systemic inflammatory response syndrome and multiple organ failure. CIP is a frequent and serious complication of intensive care that delays weaning from mechanical ventilation and increases mortality. The pathogenesis of CIP is not well understood and no specific therapy is available. The aim of this project was to use nerve excitability testing to investigate the changes in axonal membrane properties occurring in CIP. Ten patients (aged 37-76 years; 7 males, 3 females) were studied with electrophysiologically proven CIP. The median nerve was stimulated at the wrist and compound action potentials were recorded from abductor pollicis brevis muscle. Strength-duration time constant, threshold electrotonus, current-threshold relationship and recovery cycle (refractoriness, superexcitability and late subexcitability) were recorded using a recently described protocol. In eight patients a follow-up investigation was performed. All patients underwent clinical examination and laboratory investigations. Compared with age-matched normal controls (20 subjects; aged 38-79 years; 7 males, 13 females), CIP patients exhibited reduced superexcitability at 7 ms, from -22.3 +/- 1.6% to -7.6 +/- 3.1% (mean +/- SE, P approximately 0.0001) and increased accommodation to depolarizing (P < 0.01) and hyperpolarizing currents (P < 0.01), indicating membrane depolarization. Superexcitability was reduced both in patients with renal failure and without renal failure. In the former, superexcitability correlated with serum potassium (R = 0.88), and late subexcitability was also reduced (as also occurs owing to hyperkalaemia in patients with chronic renal failure). In patients without renal failure, late subexcitability was normal, and the signs of membrane depolarization correlated with raised serum bicarbonate and base excess, indicating compensated respiratory acidosis. It is inferred that motor axons in these CIP patients are depolarized, in part because of raised extracellular potassium, and in part because of hypoperfusion. The chronic membrane depolarization may contribute to the development of neuropathy.

Safety of nicotine replacement therapy in critically ill smokers: a retrospective cohort study.

PURPOSE: Nicotine replacement therapy (NRT) has been used to ameliorate nicotine withdrawal in the intensive care unit (ICU). Previous cohort studies have suggested an increased mortality with NRT use: methodological problems may call into question the validity of these findings. We undertook a retrospective cohort study to determine if NRT use was associated with adverse outcomes. METHODS: This retrospective cohort study was conducted in a 30-bed, university affiliated, teaching hospital ICU. RESULTS: We identified 423 smokers admitted over 2 years, of whom 73 received transdermal NRT. Cox proportional hazard regression models, with NRT modelled as a time-varying covariate, were used to test the hypothesis that NRT was associated with an altered ICU or hospital mortality. A second analysis utilized propensity scores. The unadjusted ICU and hospital mortalities were lower for the NRT group; although both differences were non-significant. The Cox models showed that, after adjustment for APACHE risk, age, sex and alcohol use, risk associated with NRT administration was not statistically different than non-administration for both ICU (hazard ratio 0.50, [95 % CI 0.20-1.24], p = 0.14) and hospital (hazard ratio 0.95, [95 % CI 0.52-1.75], p = 0.88) mortality. Similar findings occurred with the propensity matched analysis. CONCLUSION: We were unable to demonstrate any harm associated with NRT, with the ICU model actually trending towards benefit. We conclude that a randomised, blinded, placebo controlled trial is required to assess adequately the safety and efficacy of NRT as a treatment in critically ill smokers.

Fate and clinical significance of saphenofemoral junction tributaries following endovenous laser ablation of great saphenous vein.

BACKGROUND: Unlike surgery, endovenous laser ablation (EVLA) abolishes great saphenous vein (GSV) reflux but does not specifically interrupt the GSV tributaries at the groin. The fate and clinical significance of these tributaries were assessed in a prospective study. METHODS: Eight-one legs (70 patients) underwent colour flow duplex ultrasonography 12 months after GSV ablation for primary varicose veins. Saphenofemoral junction (SFJ) reflux, tributary patency, and recurrent or residual varicosities were recorded, and Aberdeen Varicose Vein Severity Scores (AVVSS) were compared with pretreatment values. RESULTS: The GSV had recanalized without evidence of reflux in two patients. None of the 81 legs showed SFJ reflux although one or more patent tributaries were visible in 48 (59 per cent); all were competent. In 32 legs (40 per cent) there was flush GSV occlusion with the SFJ and no tributaries were detectable. One leg showed evidence of neovascularization in the groin. AVVSS values were similar in groups with or without visible tributaries, both before and after EVLA: median (interquartile range) 13.9 (7.6-19.2) before EVLA and 2.9 (0.6-4.8) at follow-up in patients with visible tributaries, and 14.9 (9.2-20.2) and 3.1 (0.8-5.1) respectively in those without. Recurrent varicosities were present in one leg only, due to an incompetent mid-thigh perforating vein. CONCLUSION: Persistent non-refluxing GSV tributaries at the SFJ did not appear to have an adverse impact on clinical outcome 1 year after successful EVLA of the GSV.

Initial experience in endovenous laser ablation (EVLA) of varicose veins due to small saphenous vein reflux.

OBJECTIVE: Conventional surgery for varicose veins due to small saphenous reflux is associated with high recurrence rates (up to 50%), many resulting from inadequate surgery. This prospective audit examines the safety and efficacy of EVLA in the treatment of this. METHOD: 65 patients (68 limbs) with varicosities due to primary or recurrent sapheno-popliteal junction (SPJ) and small saphenous vein (SSV) reflux underwent out-patient EVLA (810 nm diode laser). The SSV was ablated from mid-calf to the SPJ. Symptomatic improvement (Aberdeen Varicose Vein Severity Score [AVVSS]), time to return to normal activity, post-EVLA analgesic requirements, and complications were recorded. RESULTS: Duplex ultrasound follow-up (median 6-months) confirmed abolition of SPJ/SSV reflux in all limbs following a median total laser energy delivery of 1131J (IQR 928-1364) at an energy density of 66.3 Joules/cm (IQR 54.2-71.6). AVVSS improved from 15.4 (IQR 11.8-19.7) to 4.6 (IQR 3.2-6.7) at three months (p<0.001). Median analgesia requirement was 3 days (23% [15/65] patients required none) and the median time to normal activity was 0 (0-4) days (65% [42/65] returning to normal daily activity immediately). There were no instances of skin burns or DVT but 3 patients (4.4%) developed transient cutaneous numbness (sural nerve). 98% (64/65) patients would undergo EVLT again. CONCLUSIONS: EVLA abolished SPJ/SSV reflux in all limbs. This is likely to be more effective than conventional surgery, although long-term follow up is required. Data from a randomised control trial would be desirable.

The role of immune-enhancing diets in the management of perioperative patients.

OBJECTIVE: To review the effects of immunonutrients in the perioperative patient. DATA SOURCES: Articles and published peer-review abstracts of studies reported on immune enhancing diets in patients during the perioperative period. SUMMARY OF REVIEW: Enteral nutrition is the method of choice for substrate supplementation in patients with a normal gastrointestinal tract but who are otherWise unable to eat normally. It is also a safer, more practical and less expensive alternative to the parenteral route and is now being used successfully in previously contraindicated conditions including pancreatitis and major abdominal trauma. Advances in enteral nutrition include the development of immunonutrients which have been used to attenuate the adverse effects of starvation, illness and surgery on the architecture and function of the gastrointestinal tract, implicated in the development of multiple organ dysfunction syndrome. These agents stimulate immune function and are potentially an effective strategy in improving the outcome in the peri-operative period by reducing post-operative infections and length of hospital stay. CONCLUSIONS: Immunonutrition confers an additive benefit when compared with standard enteral and parenteral nutrient preparations in the management of perioperative malnourished patients. What is less clear is at what severity of illness this benefit begins, whether there is a significant reduction in mortality and at what point the cost benefit in the reduction in complications no longer occurs.

Haemodynamic effects of propofol: induction with 2.5 mg kg-1.

Serial measurements of haemodynamic variables were performed at 1-min intervals in nine ASA I, unpremedicated patients before and for 5 min after induction of anaesthesia with propofol 2.5 mg kg-1. End-tidal carbon dioxide concentration was maintained within the normal range. Stroke volume and left ventricular function were measured by Doppler and cross-sectional echocardiography at the aortic valve. Systemic arterial pressure was measured by automated oscillotonometry and heart rate by electrocardiograph. Stroke volume, cardiac output, systemic vascular resistance, left ventricular stroke work and rate-pressure product were calculated. There was a decrease at all time points in systolic, mean and diastolic arterial pressure. There was an initial increase in heart rate and cardiac output, with a subsequent decrease to less than baseline. There was an initial decrease in systemic vascular resistance followed by partial recovery, and a delayed decrease in left ventricular function as measured by peak aortic blood flow velocity and acceleration.

Immunonutrition in the critically ill: a systematic review of clinical outcome.

OBJECTIVE: To perform a meta-analysis addressing whether enteral nutrition with immune-enhancing feeds benefits critically ill patients after trauma, sepsis, or major surgery. DATA SOURCES: Studies were identified by MEDLINE search (1967 to January 1998) for original articles in English using the search terms "human," "enteral nutrition," "arginine," "nucleotides," "omega-3 fatty acids," "immunonutrition," "IMPACT," and "Immun-Aid." Additionally, the authors of the studies and the manufacturers of the feeds were contacted for additional information. Access to original databases was obtained for the three largest studies. STUDY SELECTION: Fifteen randomized controlled trials comparing patients receiving standard enteral nutrition with patients receiving a commercially available immune-enhancing feed with arginine with or without glutamine, nucleotides, and omega-3 fatty acids were identified by two independent reviewers (Dr. Beale and Dr. Bryg). DATA EXTRACTION: Descriptive and outcome data were extracted independently from the papers by the same two reviewers, one of whom (Dr. Bryg) analyzed the original databases. Three studies were excluded from analysis, leaving 12 studies containing 1,557 subjects, 1,482 of whom were analyzed. Main outcome measures were mortality, infection, ventilator days, intensive care unit stay, hospital stay, diarrhea days, calorie intake, and nitrogen intake. The meta-analysis was performed on an intent-to-treat basis. DATA SYNTHESIS: There was no effect of immunonutrition on mortality (relative risk = 1.05, confidence interval [CI] = 0.78, 1.41; p = .76). There were significant reductions in infection rate (relative risk = 0.67, CI = 0.50, 0.89; p = .006), ventilator days (2.6 days, CI = 0.1, 5.1; p = .04), and hospital length of stay (2.9 days, CI = 1.4, 4.4; p = .0002) in the immunonutrition group. CONCLUSIONS: The benefits of enteral immunonutrition were most pronounced in surgical patients, although they were present in all groups. The reduction in hospital length of stay and infections has resource implications.

Pharmacokinetics of meropenem in intensive care unit patients receiving continuous veno-venous hemofiltration or hemodiafiltration.

OBJECTIVE: To evaluate an intravenous meropenem dosage regimen in adult intensive care patients with acute renal failure treated by continuous renal replacement therapy. DESIGN: A prospective, clinical study. SETTING: General intensive care unit of a university hospital. PATIENTS: Ten critically ill adult patients being treated with meropenem and receiving continuous veno-venous hemofiltration (hemofiltration rates, 1-2 L/hr) (n = 5) or continuous venovenous hemodiafiltration (hemofiltration rates, 1-1.5 L/hr; dialysis rates, 1-1.5 L/hr) (n = 5) via a polyacrylonitrile hollow fiber 0.9-m2 filter. INTERVENTIONS: Patients received a meropenem dose of 1 g iv every 12 hrs as a 5-min bolus. MEASUREMENTS AND MAIN RESULTS: Meropenem concentrations were measured by high-performance liquid chromatography in serum taken at timed intervals and in ultrafiltrate/dialysate to determine serum concentration-time profiles, derive pharmacokinetic variable estimates, and determine sieving coefficients and filter clearances. The serum concentrations were examined to see whether they were above the minimum inhibitory concentrations (MICs) for pathogens that may be encountered in intensive care patients. Serum concentrations exceeded 4 mg/L (MIC90 for Pseudomonas aeruginosa) during 67% of the dosage period in all patients. Sub-MIC90 concentrations were obtained in three patients immediately before treatment and in one patient 12 hrs after treatment. Mean (SD) (n = 10) pharmacokinetic variable estimates were as follows: elimination half-life, 5.16 hrs (1.83 hrs); volume of distribution, 0.35 L/kg (0.10 L/kg); and total clearance, 4.30 L/hr (1.38 L/hr). A sieving coefficient of 0.93 (0.06) (n = 9) indicated free flow across the filter. The fraction cleared by the extracorporeal route was 48% (13%) (n = 9), which is clinically important. CONCLUSIONS: A meropenem dose of 1g iv every 12 hrs provides adequate serum concentrations in the majority of patients receiving continuous veno-venous hemofiltration or continuous venovenous hemofiltration with a 0.9-m2 polyacrylonitrile filter at combined ultrafiltrate/dialysate flow rates of up to 3 L/hr. A lower dose would not be sufficient for the empirical treatment of potentially life-threatening infections in all patients.

ICU protocol may affect the outcome of non-elective abdominal aortic aneurysm repair.

OBJECTIVES: To compare the outcome of patients undergoing non-elective abdominal aortic aneurysm repair at two hospitals under the care of a single vascular surgeon. DESIGN: Prospective and retrospective audit of 6 years of emergency and urgent infrarenal abdominal aortic aneurysm surgery. SETTING: Lewisham and North Southwark Health Authority. SUBJECTS: One hundred and forty-five patients who underwent emergency (46) or urgent (99) repair of an abdominal aortic aneurysm. PRIMARY OUTCOME MEASURE: Hospital mortality. SECONDARY OUTCOME MEASURES: Acute renal failure, intensive care and hospital length of stay distal ischaemia and return to theatre. RESULTS: Mortality was higher at hospital 2 than hospital 1 (28% vs. 9%, p = 0.0068). There was no significant difference in age, sex, cardiac history, hypertension, diabetes, smoking, renal impairment (all p > 0.05). There was no difference in operation time, blood loss and base excess at the end of surgery between the two groups (all p > 0.05). APACHE II scores on admission to ICU were similar in hospital 1 and hospital 2 (median 16 vs. 14, p > 0.03). Pulmonary artery catheters were placed in 18% of patients at hospital 1 compared with 96% at hospital 2. Patients at hospital 2 received more crystalloid (median 2990 vs. 2300 ml+, more colloid (median 4775 vs. 1500 ml), and more inotropes (median 1 vs. 0) than those at hospital 1 in their first 24 h on ICU (all p < 0.001). The volume of urine passed in the first 24 h was similar (median 2410 vs. 2000 ml, p = 0.12) yet the incidence of acute renal failure was higher at hospital 2 compared with hospital 1 (30% vs. 6%, p = 0.001). ICU length of stay of survivors was longer at hospital 2 (median 3 vs. 2 days, p = 0.0018) as was hospital length of stay (median 17.5 vs. 12 days, p = 0.0002). CONCLUSIONS: The outcome at both hospitals is at least as good as other reported series, but it is interesting to note that the hospital which used less pulmonary artery catheters and less intervention (in the form of colloid and inotropes) showed a reduced mortality. These data may be important in assessing the different therapeutic strategies employed postoperatively in the ICU.

Effects of normothermia versus hypothermia on extravascular lung water and serum cytokines during cardiopulmonary bypass: a randomized, controlled trial.

OBJECTIVE: To evaluate the influence of perfusion temperature on the systemic effects of cardiopulmonary bypass (CPB), including extravascular lung water index (EVLWI), and serum cytokines. DESIGN: Prospective, randomized, controlled study. SETTING: Cardiothoracic intensive care unit of a university hospital. PATIENTS: Patients undergoing elective coronary artery bypass grafting. INTERVENTIONS: Twenty-one patients undergoing elective coronary artery bypass grafting were randomly assigned to receive either normothermic bypass (36 degrees C, n = 8) with intermittent antegrade warm blood cardioplegia (IAWBC), or hypothermic (32 degrees C, n = 13) CPB with cold crystalloid cardioplegia. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure, heart rate, cardiac output, systemic vascular resistance, mean pulmonary arterial pressure, and pulmonary vascular resistance were determined at baseline, i.e., after induction of anesthesia but before sternal opening (T-1), at arrival in the intensive care unit (T0), and 4 hrs (T4), 8 hrs (T8), and 24 hrs (T24) after surgery. EVLWI, intrathoracic blood volume index (ITBVI), and EVLW/ITBV ratio were obtained by using thermal dye dilution utilizing an arterial thermistor-tipped fiberoptic catheter and were recorded at T-1, T0, T4, T8, and T24. Serial blood samples for cytokine measurements were obtained at each hemodynamic measurement time point. Before, during, and after CPB, there were no differences in the conventional hemodynamic measurements between the groups. There were no changes in EVLWI up to T8 in either group. Furthermore, no change in the ratio EVLW/ITBW was observed between the groups at any time, further indicating the absence of a change in pulmonary permeability. Plasma levels of interleukin-6, tumor necrosis factor-alpha, and interleukin-10 increased during and after CPB, independently of the perfusion temperature. CONCLUSION: Normothermic CPB is not associated with additional inflammatory and related systemic adverse effects regarding cytokine production and EVLWI as compared with mild hypothermia. The potential temperature-dependent release of cytokines and subsequent inflammation has not been observed and normothermic CPB may be seen as a safe technique regarding this issue.

A comparison of cisatracurium (51W89) and atracurium by infusion in critically ill patients.

OBJECTIVE: To evaluate and compare the safety and efficacy of cisatracurium (51W89) and atracurium administered by continuous infusion to critically ill patients requiring neuromuscular blocking agents to facilitate mechanical ventilation. DESIGN: Open, randomized, multicenter study of patients receiving cisatracurium or atracurium infusion to facilitate mechanical ventilation. SETTING: Five university teaching hospital intensive care units in the United Kingdom. PATIENTS: Sixty-one adult patients requiring neuromuscular blocking agents to facilitate mechanical ventilation. INTERVENTIONS: Bolus doses followed by continuous infusions of cisatracurium or atracurium were administered. Onset, maintenance, and recovery of neuromuscular blockade were measured, using transcutaneous ulnar nerve stimulation and an accelerometer. MEASUREMENTS AND MAIN RESULTS: Forty patients received cisatracurium (mean duration 48.1 +/- 4.2 [SEM] hrs), and 21 patients received atracurium (mean duration 46.1 +/- 5.8 hrs). The infusion rate for patients receiving cisatracurium was 3.1 +/- 0.2 microg/kg/min, and for patients receiving atracurium 10.4 +/- 0.9 microg/kg/min. There were no significant differences in mean times to 70% recovery of Train-of-Four ratio (cisatracurium 60 mins, atracurium 57 mins), although there was considerable interpatient variation (20 to 175 mins with cisatracurium vs. 35 to 85 mins with atracurium). One patient who received cisatracurium exhibited intermittent bronchospasm during and after the study period. CONCLUSIONS: Cisatracurium, an isomer of atracurium, appears to be a suitable agent for providing muscle relaxation in critically ill patients.