Measuring nutrition-related outcomes in a cohort of multi-trauma patients following intensive care unit discharge.

BACKGROUND: Functional recovery is an important outcome for those who survive critical illness. The present study aimed to assess nutrition provision and nutrition-related outcomes in a multi-trauma cohort following intensive care unit (ICU) discharge. METHODS: The present study investigated a prospective cohort of patients discharged from an ICU, who had been admitted because of major trauma and required mechanical ventilation for at least 48 h. Nutrition-related outcomes, including body weight, quadriceps muscle layer thickness (QMLT), handgrip strength and subjective global assessment, were recorded on ICU discharge, days 5-7 post-ICU discharge and then weekly until hospital discharge. Nutrition intake was recorded for 5 days post-ICU discharge. Unless otherwise stated, data are presented as the mean (SD). RESULTS: Twenty-eight patients [75% males, 55 (22.5) years] were included. Intake met 64% (28%) of estimated energy and 72% (32%) of protein requirements over the 5 days post-ICU discharge, which was similar to over the ICU admission. From ICU admission to hospital discharge, the mean reduction in weight was 4.2 kg (95% confidence interval = 2.2-6.3, P < 0.001) and after ICU discharge, the mean reduction in weight and QMLT was 2.6 kg (95% confidence interval = 1.0-4.2, P = 0.004) and 0.23 cm (95% confidence interval = 0.06-0.4, P = 0.01), respectively. CONCLUSIONS: Patients received less energy and protein than estimated requirements after ICU discharge. Weight loss and reduction in QMLT also occurred during this period.

Clinical prediction of weaning and extubation in Australian and New Zealand intensive care units.

Our objective was to describe, in Australian and New Zealand adult intensive care units, the relative frequency in which various clinical criteria were used to predict weaning and extubation, and the weaning methods employed. Participant intensivists at 55 intensive care units completed a self-administered questionnaire, using visual analogue scales (0 = not at all predictive, 10 = perfectly predictive, not used = null score) to record the perceived utility of 30 potential predictors. Survey response rate was 71% (164/230). Those variables thought most predictive of weaning readiness were respiratory rate (median score 8.0, interquartile range 7.0 to 8.6) effective cough (7.3, 5.9 to 8.2) and pressure support setting (7.2, 6.0 to 8.0). The most highly rated predictors of extubation success were effective cough (8.0, 7.0 to 9.0), respiratory rate (8.0, 7.0 to 8.5) and Glasgow Coma Score (7.9, 6.1 to 8.3). Variables perceived least predictive of weaning and extubation success were P0.1, Acute Physiological and Chronic Health Evaluation score II, mean arterial pressure, electrolytes and maximum inspiratory pressure (individual median scores < 5). Most popular clinical criteria were those perceived to have high predictive accuracy, both for weaning (respiratory rate 96%, pressure support setting 94% and Glasgow coma score 91%) and extubation readiness (respiratory rate 98%, effective cough 94% and Glasgow Coma Score 92%). Weaning mostly employed pressure support ventilation (55%), with less use of synchronised intermittent mandatory ventilation (32%) and spontaneous breathing trials (13%). Classic ventilatory performance predictors including respiratory rate and effective cough were reported to be of greater clinical utility than other more recently proposed measures.

Ventilation and weaning practices in Australia and New Zealand.

Using a one-day prospective point prevalence design, this study aimed to characterise the current practice of mechanical ventilation and weaning in Australian and New Zealand intensive care units. During 2005, a bi-national one-day survey of 55 intensive care units found the point-prevalence of mechanical ventilation to be 284/491(58%). Common modes used were synchronised intermittent mandatory ventilation with pressure support, pressure support ventilation (each 116/284, 41%) and pressure-control modes (48/284, 17%). Relative to volume-control modes, pressure-control was more frequently used for patients with respiratory disease (odds ratio 4.7, 95% confidence interval 2.4 to 9.2, P <0.001) or greater severity of illness (odds ratio 1.7, 95% confidence interval 1.1 to 2.6, P = 0.01, per five-point increment in the maximum sequential organ failure score). Excluding cardiothoracic surgery patients, the Kaplan-Meier estimated median total ventilation duration was 1.9 days (interquartile range 0.8 to 6.8 days). Apart from 24/255 (9.4%) patients who received only pressure support ventilation, weaning methods (attempted in 255 patients, 29 prior deaths) included: change to pressure support ventilation (186/255, 73%), T-piece (31/255, 12%) or other methods (14/255, 5.5%). The point prevalence of mechanical ventilation was greater than comparable international studies. Australian and New Zealand intensive care unit ventilatory practices are similar, but differ substantially from published international survey results, due to a near absence of assist/control, prominent use of pressure-control modes and a preference forpressure support ventilation weaning as opposed to T-piece.

Update in computer-driven weaning from mechanical ventilation.

Weaning from mechanical ventilation is a complex process requiring assessment and interpretation of both objective and subjective clinical parameters. For many years, automated computerised systems for various medical processes, including respiratory management, have been proposed to optimise decision-making and reduce variation amongst clinicians. SmartCare/PS, available since 2003 as a software application for the EvitaXL ventilator (Dräger Medical AG & Co. KG, Lübeck, Germany), is one of the first such ventilator systems to be made commercially available. SmartCare/PS can be described as a knowledge-based weaning system, which adjusts pressure support based on measurement of the patient's respiratory status, specifically the spontaneous respiratory rate, tidal volume and end-tidal carbon dioxide with the aim of optimising the weaning process. The primary proposed advantage of this system is an ability to provide management of ventilatory weaning through continuous physiological monitoring and real-time interventions. The relatively small number of available clinical studies indicate the system is able to deliver appropriate ventilation during pressure support weaning from both short-term and prolonged ventilation. Of potential clinical note, a recent study suggested that use of SmartCare/PS might be associated with useful reductions in the duration of weaning compared to existing clinical practice using weaning protocols. One recently published randomised trial supports this conclusion. However, given the known large variation in international critical care ventilatory practices further randomised trials are desirable.

The microbiology and outcome of sepsis in Victoria, Australia.

We analysed data from 33741 patients with ICD-10-AM-defined sepsis from an Australian hospital morbidity dataset to investigate the relationships between specific types of organisms, potential risk factors for infection, organ dysfunction, ICU utilization and hospital mortality. A total of 24% of patients received some of their care in an intensive care unit, and the overall hospital mortality rate was 18%. Gram-positive bacteria were isolated in 27% of cases and Gram-negative bacteria in 20%. Sepsis due to Staphylococcus aureus was associated with vascular and joint devices whereas Pseudomonas aeruginosa and Gram-negative rods were more common with genitourinary devices and lymphoproliferative disease. Sepsis-associated organ dysfunction most commonly involved the respiratory system, followed by the renal and circulatory systems. These patterns may provide useful clues to the pathogenesis and therapy of this often fatal syndrome which is a major ongoing problem for hospitalized patients.

Antibiotic prescribing in response to bacterial isolates in the intensive care unit.

This study aimed to identify potential knowledge-performance gaps in antibiotic prescribing for bacterial isolates in the Intensive Care Unit (ICU) in order to guide the development of interventions such as antibiotic policies, decision support, and improved systems for communication between the laboratory and the bedside. A prospective observational cohort study of all patients admitted to a mixed medical/surgical ICU was undertaken over a six-month period in an Australian adult tertiary hospital. From a cohort of 524 patients, 108 had 303 isolates that were eligible for inclusion. Overall, 14.3% and 30.8% of sterile and non-sterile isolates respectively were associated with inadequate initial antibiotic therapy after identification of the bacteria. After sensitivity results were available inadequate directed therapy was observed in 4.0% and 21.3% of sterile and non-sterile isolates respectively. Problems were most commonly associated with isolates of Pseudomonas spp., Stenotrophomonas spp., Acinetobacter spp., S. aureus, enterococci and group III Enterobacteriaceae. Inadequate antibiotic therapy was found to be independently associated with prolonged length of ICU stay. Narrower spectrum antibiotic therapy was potentially available for 30% of isolates after sensitivity results were known. We conclude that there is scope to improve antibiotic prescribing in the ICU by providing clinicians with access to information regarding local susceptibility patterns and intrinsic resistance of bacteria, and spectra of antibiotic cover. Timely notification of laboratory results at the point of care may also facilitate improved prescribing performance.

Blood usage in an Australian intensive care unit: have we met best practice goals?

The transfusion of blood products, especially red cell concentrates, in critically ill patients is controversial and benefits of red cell concentrate transfusion in these patients have not been clearly demonstrated. We performed a prospective observational study to compare best evidence to actual practice of red cell concentrate and other blood product administration in an intensive care unit (ICU) in a university-associated tertiary hospital. All primary admissions during a 28-day period were included in the study and data collected included transfusion of red cells and blood products, patient demographics and ICU and hospital outcome. One hundred and seventy-five admissions were studied; 44% followed cardiac surgery. Forty-one patients (23%) received red cell concentrates in ICU, with 120 units transfused in 61 separate episodes. Other blood product usage was minimal. One third (20/61) of red cell concentrate transfusion episodes were of a single unit. The mean (+/- SD) pre-transfusion haemoglobin was 7.9 +/- 1.1 g/dl. Despite transfusion, such patients left ICU with a lower haemoglobin concentration compared with untransfused ICU patients (9.5 +/- 1.0 versus 10.5 +/- 2.1 g/dl; P < 0.001). Cardiac surgical patients received similar red cell transfusion to general ICU patients. Univariate analysis showed no significant difference in mortality between patients who did or did not receive red cell concentrate transfusion (P = 0.17). However, red cell concentrate transfusion was associated with a reduced adjusted mortality both in ICU (OR 0.13, 95% CI 0.02-0.73) and in hospital at 28 days (OR 0.10, 95% CI 0.02-0.58). The low red cell concentrate and blood product usage in our ICU were consistent with restrictive transfusion practice and selective red cell concentrate transfusion was associated with reduced mortality.

Relationship of anti-GM-CSF antibody concentration, surfactant protein A and B levels, and serum LDH to pulmonary parameters and response to GM-CSF therapy in patients with idiopathic alveolar proteinosis.

BACKGROUND: Conventional measures of the severity of alveolar proteinosis (AP) include alveolar-arterial oxygen gradient ([A - a]DO(2)), vital capacity (VC), and carbon monoxide transfer factor (TLCO), but alternative serological measures have been sought. Granulocyte-macrophage colony stimulating factor (GM-CSF) neutralising autoantibody is found in patients with idiopathic acquired AP. We have investigated the interrelationships between the levels of this antibody and those of surfactant protein (SP)-A and -B, lactate dehydrogenase (LDH), and conventional measures of disease severity, and the capacity of these parameters to predict the response to rhGM-CSF treatment. METHODS: Blood levels of anti-GM-CSF antibodies, SP-A, SP-B, LDH, and [A - a]DO(2), VC, and TLCO were measured before rhGM-CSF treatment and every 2 weeks thereafter in 14 patients with AP. RESULTS: At baseline, high levels of anti-GM-CSF antibodies and increased SP-A and SP-B levels were seen in all patients, and LDH was raised in 83%. SP-A was highly correlated with [A - a]DO(2), VC, and TLCO (p

The influence of a blood conserving device on anaemia in intensive care patients.

The contribution of iatrogenic blood loss through diagnostic testing to the anaemia of critical illness remains controversial. We measured the effect of an arterial line blood conservation device upon blood loss and anaemia in adult intensive care patients. This randomized controlled trial of 160 patients in a major Intensive Care Unit (ICU) compared a blood conservation device (Venous Arterial Blood Management Protection Plus, VAMP Plus system, Baxter Healthcare) (VAMP group) to a standard arterial pressure line set attached to an arterial catheter (control group). The primary outcome measured was the change in haemoglobin concentration (Hb) during each patient's ICU admission and the volume of blood lost through diagnostic testing in ICU was also recorded. Both groups of 80 patients were matched for age, gender, severity of illness (APACHE II), baseline Hb on entry and ICU length of stay. Both groups had a similar (median [range]) change in Hb during ICU admission (VAMP-7 [-84 to +21] g/l; Control -4 [-67 to +40] g/l; P = 0.33). The VAMP patients lost significantly less blood for diagnostic testing while in ICU (VAMP 63 [0 to 787] ml; Control 133 [7 to 1227] ml; P = 0.001). We conclude that the VAMP Plus system significantly reduced iatrogenic blood loss in critically ill patients, but this reduction did not affect the fall in Hb that accompanies critical illness.

Chest physiotherapy for the prevention of ventilator-associated pneumonia.

OBJECTIVE: Pneumonia is an important complication in patients who are intubated and mechanically ventilated, when it is commonly referred to as ventilator-associated pneumonia (VAP). Since VAP may be contributed to by impaired sputum clearance, we studied whether chest physiotherapy designed to enhance sputum clearance decreases the occurrence of VAP. DESIGN: Prospective controlled systematic allocation trial. SETTING: Tertiary teaching hospital ICU. PATIENTS AND PARTICIPANTS: Sixty adult patients intubated and mechanically ventilated for at least 48 h. INTERVENTIONS: Chest physiotherapy (intervention group) or sham physiotherapy (control group). MEASUREMENTS AND RESULTS: Control and intervention groups were well matched for age, sex, and admission PaO(2)/FiO(2) ratio, APACHE II score, and Glasgow Coma Score. There were no differences in the duration of mechanical ventilation, length of stay in ICU or mortality. VAP was assessed daily by combined clinical assessment and the clinical pulmonary infection score (CPIS). VAP occurred in 39% (14/36) of the control group and 8% (2/24) of the intervention group (OR = 0.14, 95% CI 0.03 to 0.56, P = 0.02). After adjustment was made by logistic regression for other important variables (APACHE II score, duration of mechanical ventilation, presence of tracheostomy, and GCS score), chest physiotherapy was independently associated with a reduced occurrence of VAP (adjusted OR = 0.16, 95% CI 0.03 to 0.94, P = 0.02). CONCLUSIONS: In this small trial, chest physiotherapy in ventilated patients was independently associated with a reduction in VAP. This suggested benefit of physiotherapy in prevention of VAP requires confirmation with a larger randomised controlled trial.

Therapeutic efficacy of granulocyte-macrophage colony-stimulating factor in patients with idiopathic acquired alveolar proteinosis.

Alveolar proteinosis (AP) is characterized by excessive surfactant accumulation, and most cases are of unknown etiology. Standard therapy for AP is whole-lung lavage, which may not correct the underlying defect. Because the hematopoietic cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) is required for normal surfactant homeostasis, we evaluated the therapeutic activity of GM-CSF in patients with idiopathic AP. Fourteen patients received 5 microg/kg/d GM-CSF for 6 to 12 wk with serial monitoring of the alveolar-arterial oxygen gradient ([A-a]DO2), diffusing capacity of carbon monoxide, computed tomographic scans, and exercise testing. Patients not responding to 5 microg/kg/d GM-CSF underwent stepwise dose escalation, and responding patients were retreated at disease recurrence. Stored pretreatment sera were assayed for GM-CSF-neutralizing autoantibodies. According to prospective criteria, five of 14 patients responded to 5 microg/kg/d GM- CSF, and one of four patients responded after dose escalation (20 microg/kg/d). The overall response rate was 43% (mean improvement in [A-a]DO2 = 23.2 mm Hg). Responses lasted a median of 39 wk, and were reproducible with retreatment. GM-CSF was well-tolerated, with no late toxicity seen. The only treatment-related factor predictive of response was GM-CSF-induced eosinophilia (p = 0.01). Each of 12 patients tested had GM-CSF-neutralizing autoantibodies present in pretreatment serum. We conclude that GM- CSF has therapeutic activity in idiopathic AP, providing a potential alternative to whole-lung lavage.

Plasma granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor levels in critical illness including sepsis and septic shock: relation to disease severity, multiple organ dysfunction, and mortality.

OBJECTIVE: To define the circulating levels of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) during critical illness and to determine their relationship to the severity of illness as measured by the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the development of multiple organ dysfunction, or mortality. DESIGN: Prospective cohort study. SETTING: University hospital intensive care unit. PATIENTS: A total of 82 critically ill adult patients in four clinically defined groups, namely septic shock (n = 29), sepsis without shock (n = 17), shock without sepsis (n = 22), and nonseptic, nonshock controls (n = 14). INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: During day 1 of septic shock, peak plasma levels of G-CSF, interleukin (IL)-6, and leukemia inhibitory factor (LIF), but not GM-CSF, were greater than in sepsis or shock alone (p < .001), and were correlated among themselves (rs = 0.44-0.77; p < .02) and with the APACHE II score (rs = 0.25-0.40; p = .03 to .18). G-CSF, IL-6, and UF, and sepsis, shock, septic shock, and APACHE II scores were strongly associated with organ dysfunction or 5-day mortality by univariate analysis. However, multiple logistic regression analysis showed that only septic shock remained significantly associated with organ dysfunction and only APACHE II scores and shock with 5-day mortality. Similarly, peak G-CSF, IL-6, and LIF were poorly predictive of 30-day mortality. CONCLUSIONS: Plasma levels of G-CSF, IL-6, and LIF are greatly elevated in critical illness, including septic shock, and are correlated with one another and with the severity of illness. However, they are not independently predictive of mortality, or the development of multiple organ dysfunction. GM-CSF was rarely elevated, suggesting different roles for G-CSF and GM-CSF in human septic shock.

Continuous plasmafiltration in sepsis syndrome. Plasmafiltration in Sepsis Study Group.

OBJECTIVE: To assess the effect of plasmafiltration (PF) on biochemical markers of inflammation, cytokines, organ dysfunction, and 14-day mortality in human sepsis. DESIGN: Multicenter, prospective, randomized, controlled clinical trial. SETTING: Seven university-affiliated intensive care units. PATIENTS: Thirty patients (22 adults, eight children) with new (<24 hrs) clinical evidence of infection and sepsis syndrome were enrolled. Fourteen of 30 (nine adults, five children) were randomized to PF. INTERVENTIONS: All patients received protocol-driven supportive intensive care, and those randomized to PF received continuous plasma exchange for 34 hrs using a hollow-fiber plasma filter. MEASUREMENTS AND MAIN RESULTS: Illness severity and risk of death were calculated with the Pediatric Risk of Mortality (children) and the Acute Physiology and Chronic Health Evaluation II (adults) scales. Plasma samples (0, 6, 24, and 48 hrs) were assayed for acute-phase proteins (albumin, globulin, C-reactive protein, alpha1-antitrypsin, haptoglobin), inflammatory mediators (complement fragment C3, thromboxane B2), and cytokines (interleukin-6, granulocyte colony-stimulating factor, leukemia inhibitory factor). Sieving coefficients were estimated from filtrate concentrations at 3 hrs. The two groups were matched for incidence of septic shock (13 of 14 vs. 11 of 16), refractory shock (three of 14 vs. six of 16), bacteremia (six of 14 vs. five of 16), severity of illness, and calculated risk of death (0.68 vs. 0.64). There was no difference in mortality. Eight of 14 PF patients (57%) and eight of 16 controls (50%) survived for 14 days (p = .73, Fisher's exact test). Multiple logistic regression revealed age (odds ratio, 16.4:1; 95% confidence interval, 2.12-infinity) and shock (10.6:1; 1.32-infinity) as significant predictors of death; plasmafiltration was associated with a nonsignificant reduction in the risk of death (odds ratio, 1.78:1; 95% confidence interval, 0.20-18.1). The mean (SD) number of organs failing in the first 7 days in the PF group was 2.57 (0.94) vs. 2.94 (0.85) in controls (p = .37, Mann-Whitney U test). Both groups had similarly elevated plasma concentrations of all inflammatory mediators except complement fragment C3 at study entry. Leukemia inhibitory factor was detectable in four patients only. PF did not influence mean concentrations of interleukin-6, granulocyte colony-stimulating factor, thromboxane B2, total white cell count, neutrophil count, or platelet count, but it was associated with significant reductions of alpha1-antitrypsin, haptoglobin, C-reactive protein, and complement fragment C3 in the first 6 hrs (p < .05). The sieving coefficients for all inflammatory mediators approached unity. CONCLUSIONS: PF caused a significant attenuation of the acute-phase response in sepsis. There was no significant difference in mortality, but there was a trend toward fewer organs failing in the PF group that suggests that this procedure might be beneficial.

Recognition and management of catheter-induced pulmonary artery rupture.

BACKGROUND: Catheter-induced pulmonary artery rupture is a well-recognized complication of invasive monitoring, but the risk has not diminished. Although commonly associated with cardiopulmonary bypass, injuries also occur in intensive care. Definitive proof requires pulmonary angiography or autopsy. Many cases are never reported, and lesser injuries are probably under-diagnosed. METHODS: Seven cases fulfilling accepted diagnostic criteria discovered over 2 years are described in four groups illustrating the common modes of presentation: hemoptysis with hypoxemia, exsanguination, delayed recurrent hemorrhage, and bleeding with cardiopulmonary bypass. RESULTS: One patient had a planned elective operation deferred. Four patients were being monitored in intensive care. Two of them died of pulmonary artery rupture. Two other patients had bleeding on weaning from cardiopulmonary bypass. One settled with conservative treatment, the other survived after extracorporeal life support. Recognition and management are discussed, emphasizing means of avoiding pulmonary resection. CONCLUSIONS: Catheter-induced pulmonary artery rupture is unavoidable. Constant awareness is essential. A plan of management is presented. Extracorporeal life support may help to avoid pulmonary resection. Early pulmonary angiography is advocated for accurate diagnosis and to enable treatment by embolization.

Attenuated hematopoietic response to granulocyte-macrophage colony-stimulating factor in patients with acquired pulmonary alveolar proteinosis.

The pathogenesis of acquired pulmonary alveolar proteinosis (PAP), a rare lung disease characterized by excessive surfactant accumulation within the alveolar space, remains obscure. Gene-targeted mice lacking the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) or the signal-transducing beta-common chain of the GM-CSF receptor have impaired surfactant clearance and pulmonary pathology resembling human PAP. We therefore investigated the hematopoietic effects of GM-CSF in patients with PAP. The hematologic response of 5 infants with congenital PAP to 5 microgram/kg/d was of normal magnitude. By contrast, despite normal expression of GM-CSF receptor alpha- and beta-common chains on peripheral blood myelomonocytic cells (n = 6) and normal binding affinity of bone marrow mononuclear cells for GM-CSF (n = 3), each of the 12 patients with acquired PAP treated displayed impaired responses to GM-CSF; 5 microgram/kg/d produced only minor eosinophilia, and doses of 7.5 to 20 microgram/kg were required to induce >/=1.5-fold neutrophil increments in the 3 patients who underwent dose-escalation. However, neutrophilic responses to 5 microgram/kg granulocyte colony-stimulating factor (G-CSF) were normal (n = 4). In vitro, the proportion of hematopoietic progenitors responsive to GM-CSF (16.1% +/- 8.9%; P = .042) or interleukin-3 (IL-3; 19.3% +/- 7.7%; P = .063), both of which utilize the beta-common chain of the GM-CSF receptor complex, were reduced among patients with acquired PAP (n = 4) compared with normal bone marrow donor controls (47.2% +/- 25.9% and 40.9% +/- 18.6%, respectively). In the one individual who had complete resolution of lung disease during the period of study, this was temporally associated with correction of this defective in vitro response to GM-CSF and IL-3 on serial assessment. These data establish that patients with acquired PAP have an associated impaired responsiveness to GM-CSF that is potentially pathogenic in the development of their lung disease. Based on these observations, we propose a model of the pathogenesis of acquired PAP that suggests the disease arises as a consequence of an acquired clonal disorder within the hematopoietic progenitor cell compartment.

A new formulation of aspirin: bioavailability and analgesic efficacy in migraine attacks.

Plasma aspirin and salicylate concentrations were followed after 600 mg of a new palatable glycinated preparation of aspirin was given to six healthy male volunteers in an attempt to investigate whether pre-gastric absorption of aspirin could occur. In each subject the drug was administered by three different routes, viz. (i) swallowed with water, (ii) dissolved sublingually and retained in the mouth, and (iii) allowed to disperse on the tongue, and then swallowed without water intake. Using the latter route of administration and the same aspirin formulation, plasma aspirin and salicylate concentrations were also followed in 10 patients during acute migraine attacks. These results were compared with those from another 10 migraineurs given 600 mg of soluble aspirin swallowed with water during attacks. Aspirin and salicylate pharmacokinetic parameters (Cmax, tmax, t1/2, Kabs and AUC) in the normal volunteers were not significantly different (p greater than 0.05) whether glycinated aspirin was swallowed with water or swallowed without water after dispersion in the mouth. However, negligible aspirin was absorbed when the glycinated preparation was retained in the mouth. In migraine patients, there was no significant difference (p greater than 0.05) between the bioavailabilities of soluble aspirin swallowed with water (AUC = 5.7 +/- 2.3 mg h/l) and glycinated aspirin swallowed without water (AUC = 4.4 +/- 1.6 mg h/l). There also was no significant difference (p greater than 0.05) when the time courses of pain relief were compared, both treatments being associated with a significant (p less than 0.01) analgesic effect. The glycinated aspirin was thus bioequivalent to swallowed aspirin but has no advantages for migraineurs over soluble aspirin if water is readily available for self-administration.