Ibuprofen Treatment Reduces the Neuroinflammatory Response and Associated Neuronal and White Matter Impairment in the Growth Restricted Newborn.

Intrauterine growth restriction (IUGR) is a condition where the fetus does not achieve optimal growth, commonly caused by placental insufficiency. The chronic decrease in blood flow restricts oxygen and nutrient supply to the fetus, which can damage numerous organ systems, with the fetal brain being particularly vulnerable. Although white matter and neuronal injury are evident in IUGR infants, the specific mechanisms underlying these changes are poorly understood. Inflammation is considered to be a main driver in exacerbating brain injury. Using a spontaneous piglet model of IUGR, we aim to determine whether administration of the anti-inflammatory drug ibuprofen will decrease inflammation at postnatal day 4 (P4). The treatment group received ibuprofen (20 mg/kg/day on day 1 and 10 mg/kg/day on days 2 and 3) in piglet formula during the morning feed each day and brains examined on P4. Markers of inflammation, apoptosis, cell proliferation, neuronal injury, and white matter injury were examined. Ibuprofen treatment ameliorated the increase in numbers of microglia and astrocytes in the parietal cortex and white matter tracts of the IUGR piglet brain on P4 as well as decreasing proinflammatory cytokines. Ibuprofen treatment prevented the reduction in apoptosis, neuronal cell counts, and myelin index in the IUGR piglets. Our findings demonstrate ibuprofen reduces the inflammatory response in the IUGR neonatal brain and concurrently reduces neuronal and white matter impairment.

Facing acid-base disorders in the third millennium - the Stewart approach revisited.

Acid-base disorders are common in the critically ill. Most of these disorders do not cause harm and are self-limiting after appropriate resuscitation and management. Unfortunately, clinicians tend to think about an acid-base disturbance as a "disease" and spend long hours effectively treating numbers rather than the patient. Moreover, a sizable number of intensive-care physicians experience difficulties in interpreting the significance of or understanding the etiology of certain forms of acid-base disequilibria. Traditional tools for interpreting acid-base disorders may not be adequate for analyzing the complex nature of these metabolic abnormalities. Inappropriate interpretation may also lead to wrong clinical conclusions and incorrectly influence clinical management (eg, bicarbonate therapy for metabolic acidosis in different clinical situations). The Stewart approach, based on physicochemical principles, is a robust physiological concept that can facilitate the interpretation and analysis of simple, mixed, and complex acid-base disorders, thereby allowing better diagnosis of the cause of the disturbance and more timely treatment. However, as the concept does not attach importance to plasma bicarbonate, clinicians may find it complicated to use in their daily clinical practice. This article reviews various approaches to interpreting acid-base disorders and suggests the integration of base-excess and Stewart approach for a better interpretation of these metabolic disorders.

Evaluation of the Pneupac Ventipac portable ventilator in critically ill patients.

We assessed adequacy of ventilation in 20 critically ill patients with multiple organ failure using a Pneupac Ventipac portable ventilator and the effects on patients' haemodynamic stability. Baseline data were recorded over 15 min for a range of respiratory, haemodynamic and oxygen transport variables during ventilation with a standard intensive care ventilator (Engström Erica). Patients were then ventilated for 40 min using the portable ventilator. Finally, they were ventilated for a further 40 min using the standard intensive care ventilator. Heart rate, arterial and pulmonary artery pressures were recorded at 5-min intervals throughout the study period. Cardiac index and other haemodynamic data derived from a pulmonary artery catheter were recorded at 20-min intervals. Blood gas analysis was performed and oxygen transport data (oxygen delivery, oxygen consumption and physiological shunt) were calculated at the end of each of the three periods of ventilation. In general, no significant adverse effects of ventilation using the portable ventilator were observed for any of the variables studied. Arterial PO(2) increased significantly during ventilation with the portable ventilator, reflecting the use of a higher inspired oxygen fraction during this part of the study. Oxygen consumption decreased significantly in one patient during ventilation by the portable ventilator although none of the other variables measured in this patient was altered. We conclude that ventilation of critically ill patients using the Pneupac Ventipac portable ventilator was safe, satisfactory and associated with minimal adverse effects on respiratory, haemodynamic and oxygen transport variables.

Transfusion requirements during continuous veno-venous haemofiltration: -the importance of filter life.

OBJECTIVE: To investigate the relationship between loss of haemofilter circuits due to blood clots and requirement for blood transfusion in intensive care patients. DESIGN: Retrospective case note review. SETTING: A British, nine-bed, tertiary, medical and surgical intensive care unit (ICU) serving a 950-bed university teaching hospital. PATIENTS: Thirty-three ICU patients requiring haemofiltration for more than 48 h. Thirty-three comparison patients requiring 7 or more days of intensive care, without haemofiltration. METHODS: ICU, haemofiltration and haematology records were examined retrospectively. Note was taken of demographic data, daily haemoglobin concentrations and the dates and numbers of blood transfusions and haemofilter clots. RESULTS: The study groups did not differ significantly in terms of age, sex and length of ICU stay. Haemofiltered patients had higher APACHE II scores (21 vs 15, p = 0.006), lower haemoglobin concentrations (102 vs 110 g/l, p = 0.0001) and higher blood transfusion rates (1.1 vs 0.3 units/day, p < 0.0001) when compared to the non-haemofiltered group. There was a positive correlation between haemofilter blood clot rate and blood transfusion rate (r = 0.48). More blood was transfused on days when haemofilter blood clots occurred than on days when no haemofilter clot occurred (1.0 vs 0.59 units, p = 0.03). CONCLUSION: Haemofiltration is associated with an increased requirement for transfusion of blood. The temporal relationship between occurrence of haemofilter blood clots and transfusion of blood suggests that haemofilter lifespan may be an important determinant of this.

Meeting the standards for interhospital transfer of adults with severe head injury in the United Kingdom.

In December 1996, the Association of Anaesthetists of Great Britain and Ireland produced a series of recommendations outlining the safe conduct of interhospital transfers for patients with acute head injuries. We assessed the current ability of UK hospitals to implement these recommendations and opinions on the formation of transfer teams, using a postal questionnaire. This was sent to all Royal College of Anaesthetists tutors, 268 of whom replied (94% response rate). Of the hospitals surveyed, 208 received adult head-injury patients but did not have on-site neurosurgical facilities. In 171 (86.8%) of these hospitals, senior house officers could be expected to accompany the patient during subsequent transfer. The majority of hospitals (192, 92.3%) were able to monitor ECG, pulse oximetry and blood pressure during the journey, but only 97 (46.6%) had facilities to monitor end tidal carbon dioxide levels. As a result of the anaesthetist's involvement in the transfer, emergency operating could be delayed in 169 (81.3%) hospitals. One hundred and fifty-eight (76%) respondents thought that the formation of transfer teams to transport critically ill patients would have some merit. Hospitals are responding to the published guidelines, but improvements are still needed in levels of equipment and insurance provision, along with the identification of a designated consultant at each hospital with responsibility for transfers.

Comparison of lactate and bicarbonate buffered haemofiltration fluids: use in critically ill patients.

OBJECTIVE: To compare acid-base balance, lactate concentration, and haemodynamic and O2 transport variables during haemofiltration with replacement fluid containing 44.5 mmol/l Na+ lactate or 40 mmol/l Na+ HCO3- and 3 mmol/l lactic acid. DESIGN: A prospective, randomized trial. SETTING: A multidisciplinary, adult intensive care unit in a university hospital. PATIENTS: Forty acidotic patients who required haemofiltration, were dependent on mechanical ventilation, and had PA catheters in situ. INTERVENTIONS: During haemofiltration patients received lactate or bicarbonate replacement fluid at a mean rate of 1.7 l/h (SD 0.3). Arterial blood gases, plasma lactate, and haemodynamic and O2 transport variables were measured before and after 12 and 24 h haemofiltration. Ultrafiltrate was collected for lactate estimation. MEASUREMENTS AND MAIN RESULTS: As means (SD). The net gain of lactate was 63 mmol/h (12 mmol) with Na+ lactate and 0 mmol/h (0.3 mmol) with Na+ HCO3-. There was a significant increase in pH and [lactate] in both groups, but [lactate] was higher in patients receiving lactate. Twenty-one patients survived to ICU discharge, these patients were significantly less acidotic after filtration (lactate group: 0 h: pH 7.23 (0.09), [lactate] 2.4 mmol/l (1.7); 12 h: pH 7.34 (0.09), [lactate] 4.7 mmol/l (2.4); 24 h: pH 7.36 (0.07), [lactate] 4.7 mmol (2.7). HCO3 group: 0 h: pH 7.23 (0.09), [lactate] 2.3 (1.3); 12 h: pH 7.32 (0.06), [lactate] 2.9 mmol/l (1.8); 24 h: pH 7.35 (0.08), [lactate] 2.8 mmol/l (2.0). Base deficit: survivors: 0 h: 9 mmol/l (4); 12 h: 2 mmol/l (3). Non-survivors: 0 h: 10 mmol/l (3); 12 h: 6 mmol/l (3)). Haemodynamic and O2 transport variables were not significantly affected by treatment group or outcome. CONCLUSIONS: The degree of correction of acidosis during the first 24 h of haemofiltration was determined by patients outcome but was not affected by the substitution of bicarbonate- for lactate-containing replacement fluids.

The prognostic value of serial measurements of serum albumin concentration in patients admitted to an intensive care unit.

The prognostic value of serial measurements of serum albumin concentration during the first 72 h after admission to a general adult intensive care unit was retrospectively reviewed in 348 consecutive critically ill patients over a one year period. The accuracy of the admission APACHE II (Acute Physiology And Chronic Health Evaluation) score in correctly predicting patient outcome was compared with the serum albumin concentration measured at different times after intensive care unit admission. Multiple logistical regression analyses were performed to evaluate whether combining APACHE II and serum albumin into a unified risk index improved prognostic accuracy. Serum albumin concentration on admission was lower in non-survivors than in survivors and decreased more rapidly in non-survivors (p < 0.001). The admission serum albumin concentration was found to be an insensitive prognostic indicator. However, serum albumin measured after 24 h was as accurate as the admission APACHE II score in correctly classifying patients according to outcome. There was a good correlation between the admission APACHE II score and serum albumin measured after 24 h but not between the admission APACHE II and the admission serum albumin. Combining the APACHE II score and serial albumin concentrations into a unified risk of death equation did not improve the accuracy of outcome prediction.

Creatinine and urea clearance during continuous veno-venous haemofiltration in critically ill patients.

Urea and creatinine clearances achieved using continuous veno-venous haemofiltration were calculated in 16 critically ill patients, during 50 episodes of filtration. The effects of filter life and the volume of ultrafiltrate on these clearances were also evaluated. Clearances were calculated from urea and creatinine concentrations in blood and ultrafiltrate and the volume of ultrafiltrate produced. The overall mean (SD) urea clearance was 26.6 (6.0) ml.min-1 and the overall creatinine clearance was 30.1 (6.3) ml.min-1. The mean (SD) ultrafiltrate production was 29.6 (5.9) ml.min-1. Creatinine clearance was significantly lower in filters that failed within 24 h (filters < 24 h 27.5 (6.3) ml.min-1; filters > 24 h 32.2 (5.5) ml.min-1). The clearance of both solutes increased with increasing ultrafiltrate volume (p < 0.001). We conclude that satisfactory clearance of urea and creatinine can be achieved using continuous veno-venous haemofiltration. Increases in ultrafiltrate production lead to similar increases in urea and creatinine clearance. Prolongation of filter life may improve creatinine clearance.

Trauma audit--closing the loop.

The philosophy of medical audit and methods of data collection and statistical analysis have been extensively reviewed but less has been written about the effect of audit on medical practice. The measurement of performance is only valuable if it identifies areas of concern and stimulates appropriate change. This paper describes the work of the Salford Trauma Audit Group which has been developed at Hope Hospital, the problems that have been recognized, the strategies that have been introduced to effect change and their influence on management and outcome. Analysis of performance reveals an initial fall in adjusted mortality rate from severe injury after the introduction of resuscitation teams, the adherence to Advanced Trauma Life Support protocols and an integrated multidisciplinary approach to trauma care. Problems remain and there is continuing concern about trauma management in the hospital. This has been reinforced by performance feedback through the Trauma Audit Group which has attracted the interest of senior clinicians in several specialties.

Appraisal of percutaneous tracheostomy.

Two commercially available kits have been used to create 25 percutaneous tracheostomies, 20 using the Cook system and five using the Rapitrac system. The operation time and complication rates of these tracheostomies have been compared with those for 16 conventional tracheostomies performed for similar indications. Median operating times were 60 (range 30-105) min for conventional tracheostomy, 15 (range 8-70) min for Cook and 5 (range 3-15) min for Rapitrac systems (P less than 0.001). A significantly higher proportion of patients in the Rapitrac group had complications compared with the other two groups (P less than 0.05). The complication rate for the Cook group compared favourably with that for the conventional tracheostomy group. The Cook system of percutaneous tracheostomy is a simple, rapid and safe alternative to conventional tracheostomy.

Significance and management of intractable supraventricular arrhythmias in critically ill patients.

In a heterogeneous group of 23 critically ill patients with recurrent and intractable bouts of supraventricular arrhythmia, increases in pulmonary artery wedge pressure significantly decreased cardiac output and exacerbated respiratory failure. Most patients were eventually stabilized on a long-term iv infusion of the calcium antagonist verapamil which, with appropriate monitoring, was well tolerated. We suggest that the use of verapamil infusion may play a significant role in the management of such patients and that further studies are justified.

Some actions of sodium nitroprusside and glyceryl trinitrate on guinea-pig isolated trachealis muscle.

The smooth muscle relaxant actions of sodium nitroprusside and glyceryl trinitrate have been compared to those of aminophylline and isoprenaline on isolated guinea pig trachealis muscle. Ethacrynic acid (0.25 X 10(-4) M), an alkylator of sulphydryl groups, interacted differently with the four agents. In the presence of ethacrynic acid the concentration response curve of the muscle preparation to sodium nitroprusside and glyceryl trinitrate was shifted to the higher concentration ranges and the maximum response was severely reduced. The concentration response curve for isoprenaline was shifted to the higher concentration ranges with no change in the maximum response and the response to aminophylline was unchanged. These results argue against common intermediate sites of action involving sulphydryl groups of the four agents in guinea-pig trachealis.