High prevalence of Felis catus gammaherpesvirus 1 infection in haemoplasma-infected cats supports co-transmission.

Felis catus gammaherpesvirus 1 (FcaGHV1), a potential feline pathogen, has been identified in domestic cats from USA, Asia-Pacific and Central Europe. Transmission of FcaGHV1 during territorial encounters, a route not typical for gammaherpesviruses, is suggested by risk factor analyses from some regions. The aim of this study was to investigate the relationship between FcaGHV1 detection and risk factors, including haemoplasma co-infections, among UK cats to better understand transmission and global distribution of FcaGHV1. FcaGHV1 DNA was detected in blood samples from UK cats (11.56%; 95% confidence interval [CI], 7.47-16.84; n = 199). Logistic regression analyses showed that entire male cats were more likely to be FcaGHV1 positive than neutered male cats (odds ratio, 3.60; 95% CI, 1.22-10.46). Samples positive for DNA from any of three haemoplasma species had 19 times greater odds for testing positive for FcaGHV1 than haemoplasma negative cats in multivariable analyses after adjusting for age, sex and neuter status. Domestic cats in the UK can be infected with FcaGHV1, confirming that this virus is globally endemic. The identification of neuter status as a risk factor for FcaGHV1 detection provides further evidence to support transmission of this virus during territorial encounters and co-transmission with haemoplasmas is suggested.

A multi-centre, double-blind, placebo-controlled study of liposomal prostaglandin E1 (TLC C-53) in patients with acute respiratory distress syndrome.

OBJECTIVE: To evaluate the safety of liposomal PGE1 (TLC C-53) in patients with acute respiratory distress syndrome (ARDS), and determine its efficacy in improving oxygenation and reducing ventilator dependency. DESIGN: A multi-centre, randomized, double-blind, placebo-controlled clinical study. SETTING: Thirty-one hospitals in six European countries. PATIENTS: One hundred two patients with ARDS. INTERVENTIONS: Patients were randomized in a 2:1 ratio to receive infusions of either the study drug TLC C-53 or placebo. Infusions were given over 60 min every 6 h for 7 days. The dose of study drug started at 0.6 microg/kg per h, rising over 24 h to a maximum dose of 1.8 microg/kg per h. MEASUREMENTS AND MAIN RESULTS: Seventy patients received the study drug and 32 placebo. Sixty-nine patients (47 treatment, 22 placebo) completed the study protocol. Patients were monitored for changes in the PaO2/FIO2 ratio, changes in lung compliance, time to off-ventilator and 28-day mortality, in addition to basic haematological and haemodynamic parameters. There were no significant differences in demographics and baseline characteristics between the two groups. There were no differences in the time to off-ventilation (16 days with treatment, 16.6 days with placebo, p=0.94) or in 28-day mortality (30% with treatment, 28% with placebo, p=0.78). There was a difference in the time to achieve a PaO2/FIO2 ratio above 300 in favour of TLC C-53 (10.3 versus 26.5 days) but this was not statistically significant (p=0.23). CONCLUSIONS: TLC C-53 was generally well-tolerated but failed to reduce mortality or duration of mechanical ventilation.

Investigating the relationship between intrathoracic blood volume index and cardiac index.

OBJECTIVES: To determine whether cardiac index and intrathoracic blood volume index are "mathematically coupled" under euvolaemic conditions with increasing levels of inotropic support. DESIGN: Prospective case series. SETTING: A 14-bed general intensive care unit in a university-affiliated hospital. PATIENTS: Twelve mechanically ventilated patients, monitored with the COLD system and receiving dobutamine as inotropic support. INTERVENTION: After measuring cardiac index and intrathoracic blood volume index the rate of dobutamine infusion was increased until cardiac index rose by at least 20%. A further measurement of intrathoracic blood volume index was made at the new cardiac index. MEASUREMENTS AND RESULTS: The mean increase in cardiac index was 31.7%, compared with a mean increase in intrathoracic blood volume index of only 2.84%. CONCLUSION: Under euvolaemic conditions, raising cardiac index by increasing inotropic support does not alter intrathoracic blood volume index significantly, thus demonstrating that the two measurements are not 'mathematically coupled' under these conditions.

Assessment of cardiac preload and extravascular lung water by single transpulmonary thermodilution.

OBJECTIVE: Transpulmonary double-indicator dilution is a useful monitoring technique for measurement of intrathoracic blood volume (ITBV) and extravascular lung water (EVLW). In this study, we compared a simpler approach using single arterial thermodilution derived measurements of ITBV and EVLW with the double-indicator dilution technique. DESIGN: Prospective observational clinical study. SETTING: Surgical intensive care units of two university hospitals. PATIENTS AND METHODS: Global end-diastolic volume (GEDV) derived from single thermodilution was used for calculation of ITBV. Structural regression analysis of the first two thermo-dye dilution measurements in a derivation population of 57 critically ill patients (38 male, 19 female, 18-79 years, 56 +/- 15 years) revealed ITBV = (1.25 x GEDV)-28.4 (ml). This equation was then applied to all first measurements in a validation population of 209 critically ill patients (139 male, 70 female, 10-88 years, mean 53 +/- 19 years), and single-thermodilution ITBV (ITBV(ST)) and EVLW (EVLW(ST)) was calculated and compared to thermo-dye dilution derived values (ITBV(TD), EVLW(TD)). For inter-individual comparison, absolute values for ITBV and EVLW were normalised as indexed by body surface area (ITBVI) and body weight (EVLWI), respectively. MEASUREMENTS AND RESULTS: Linear regression analysis yielded a correlation of ITBVI(ST) = (1.05 x ITBVI(TD))-58.0 (ml/m2), r = 0.97, P < 0.0001. Bias between ITBVI(TD) and ITBVI(ST) was 7.6 (ml/m2) with a standard deviation of 57.4 (ml/m2). Single-thermodilution EVLWI (EVLWI(ST)) was calculated using ITBVI(ST) and revealed the correlation EVLWI(ST) = (0.83 x EVLWI(TD)) + 1.6 (ml/kg), r = 0.96, P < 0.0001. Bias between EVLWI(TD) and EVLWI(ST) was -0.2 (ml/kg) with a standard deviation of 1.4 (ml/kg). In detail, EVLWI(ST) systematically overestimated EVLWI(TD) at low-normal values for EVLWI and underestimated EVLWI at higher values (above 12 ml/kg). CONCLUSION: Determinations of ITBV and EVLW by single thermodilution agreed closely with the corresponding values from the double-indicator technique. Since transpulmonary single thermodilution is simple to apply, less invasive and cheaper, all these features make it a promising technique for the bedside. Nevertheless, further validation studies are needed in the future.

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.

Scanning laser Doppler is a useful technique to assess foot cutaneous perfusion during femoral artery cannulation.

BACKGROUND: Measurement of cardiac output and extravascular lung water in critically ill patients using femoral artery double-indicator dilution involves femoral artery catheterization. The potential risk of vascular compromise to the limb may be exacerbated in patients receiving vasopressors. The utility of scanning laser Doppler flowmetry to measure changes in pedal perfusion following catheterization was assessed. RESULTS: There were no significant changes in mean occlusion pressures or in cutaneous perfusion between either leg or between measurement time points, immediately after or 24 h following insertion of the catheters. CONCLUSIONS: Scanning laser Doppler flowmetry is easily used to assess changes in foot perfusion and the effect of interventions that may reduce blood flow to the skin of the foot. Femoral artery catheterization for double-indicator dilution measurements does not reduce calf occlusion pressures or foot skin perfusion in patients receiving vasopressor drugs.

A comparison of pulmonary and femoral artery thermodilution cardiac indices in paediatric intensive care patients.

We have assessed the agreement between pulmonary artery and femoral artery (COLD) thermodilution measurements of the cardiac index (Cl) in a group of paediatric intensive care patients. The COLD method gave consistently higher cardiac index values than the pulmonary artery catheter (PAC); however, the difference was small, with a mean value of 0.19 l/min-1 m-2 or 4.4% of the mean cardiac index. This difference is not clinically important and suggests that, under these circumstances, the COLD system provides an acceptable alternative to the pulmonary artery catheter for measurement of the cardiac index at the bedside.

Continuous haemodynamic monitoring in children: use of transoesophageal Doppler.

A wide range of invasive and non-invasive techniques for monitoring the haemodynamic condition of critically ill patients is now available. A general reluctance on the part of paediatric intensive care specialists to use pulmonary artery thermodilution catheters and the need for constant realignment of hand-held Doppler probes has necessitated the search for a technique which is relatively non-invasive and provides continuous information on the haemodynamic condition of critically ill paediatric patients. We sought to establish if transoesophageal Doppler fulfilled these criteria. Eleven children who had recently undergone cardiac surgery were studied. Median age was 39 months and weight 14.9 kg. Five simultaneous pairs of measurements of cardiac index (CI: thermodilution) and minute distance (MD: transoesophageal Doppler) were made, as a baseline, when each child was haemodynamically stable. Following a fluid challenge, five repeat pairs of measurements were made. The mean percentage changes for CI and MD were 16.4% (range 5.3-44%) and 16.6% (3.4-47.7%), respectively. The average coefficients of variation for measurements of CI and MD were 3.5% and 2.9%, respectively. The mean difference in percentage change between CI and MD was -0.5% (95% confidence interval for the bias -4% to 3%; limits of agreement -10.7 to +9.7%). Our study indicates that transoesophageal Doppler is reproducible, easy to use and provides clinically acceptable information when following changes in CI in haemodynamically stable paediatric patients.

Atrial fibrillation following pulse methylprednisolone therapy in an adult.

The authors believe this to be the first case report of atrial fibrillation following pulse methylprednisolone therapy in an adult. The literature regarding the complications of pulse methylprednisolone therapy is reviewed, with particular emphasis on the incidence and pathogenesis of arrhythmias.

Local analgesia for infant pyloromyotomy. Does wound infiltration with bupivacaine affect postoperative behaviour?

A series of 20 infants undergoing general anaesthesia for pyloromyotomy were studied in a randomised, blind and controlled trial to determine the postoperative behavioural and cardiorespiratory effects of wound infiltration of bupivacaine. Ten infants received bupivacaine (0.6 ml/kg, 0.25% = 1.5 mg/kg) injected intradermally into the wound during general anaesthesia and 10 infants received general anaesthesia only. Postoperatively, an independent observer assessed conscious level, crying, posture and facial expression using a simple numerical scoring system, and also recorded heart and respiratory rates over a 2-h period. Infants who had received bupivacaine were observed to have higher respiratory rates and behaviour scores, although these differences were not statistically significant. These results indicate that wound infiltration with bupivacaine offers no obvious advantage to infants following pyloromyotomy.

Role of repeated doses of oral activated charcoal in the treatment of acute intoxications.

While single dose activated charcoal is effective in preventing drug absorption, repeated doses not only prevent absorption but also can increase systemic drug clearance. The mechanism for the latter effect may involve interruption of enterohepatic recycling and/or promotion of drug exsorption from the systemic circulation into the gut lumen. A comprehensive review of reported studies in volunteer subjects and overdose patients showed that repeated dose activated charcoal markedly decreased the half-life and/or increased the clearance of a wide range of drugs. Side-effects of the treatment were infrequent, but included aspiration pneumonia, diarrhoea and constipation. The addition of laxatives to repeated dose charcoal treatment did not offer any significant increase in drug clearance and is not recommended. It is suggested that the optimal regimen for the use of repeat dose activated charcoal in acute drug intoxications is an initial dose of 75-100 g, followed by 50 g every 4 hours until the risks of systemic drug toxicity are reduced to an acceptable level.

Gastric aspirates after trauma in children.

The volumes and pH of gastric aspirates obtained from 110 children (aged 1-14 years) who underwent surgery for trauma were related to the duration of pre-operative starvation and to the interval between food and injury. Aspirates were larger in children fasted for 4-6 hours than in those fasted for up to 10 hours, and were larger in children injured within 2 hours of eating than in those in whom this interval was longer (p less than 0.05). However, 19 of 39 children (49%) starved for over 8 hours had an aspirate of more than 0.4 ml/kg, as did five of 16 children (31%) injured 3 or more hours after eating. Thus, a 'safe' interval between oral intake and induction cannot be predicted. We conclude that securing the airway by prompt tracheal intubation is the safest way to manage any child who presents for emergency anaesthesia after trauma.