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Biomedical subjects

M G Mythen

Publications and source records attributed to M G Mythen.

At least 19 recordsLinked to original sources
PubMed2006

Endotoxin immunity and the development of the systemic inflammatory response syndrome in critically ill children.

BACKGROUND: The systemic inflammatory response syndrome (SIRS) may be triggered by endotoxin. Humans have antibodies directed against the core of endotoxin (endotoxin core antibodies, EndoCAb) that appear to be protective following surgery and in sepsis. We hypothesised that children with elevated antibodies to endotoxin core would be less likely to develop SIRS in their initial period on intensive care. Because of the existing literature we defined two sub-groups according to the primary reason for ICU admission: infection and non-infection. METHODS: We recruited 139 consecutive patients admitted to a paediatric intensive care unit (PICU) with more than one organ failure for longer than 12 h as part of another study. Patients were classified on admission to PICU as having an infectious or a non-infections diagnosis. The occurrence of SIRS within 48 h of admission was recorded along with detailed clinical and demographic data, EndoCAb concentration and the potential confounding variables C-reactive protein and mannose-binding lectin. RESULTS: In the 71 patients admitted without infection (primarily post-operative and head injured) IgG EndoCAb was significantly lower in patients who developed SIRS than those who did not (72 vs. 131 MU/ml), independent of potential confounding variables. In patients with infection there was no significant difference in IgG EndoCAb between children developing SIRS and those who did not (111 vs. 80 MU/ml). CONCLUSION: Head injured and post-operative patients admitted to PICU who develop early SIRS have significantly lower serum IgG EndoCAb levels than those who do not.

Adolescent↗
PubMed2006

Just scratching the surface: varied coagulation effects of polymer containers on TEG variables.

BACKGROUND AND OBJECTIVE: Different types of polymer surfaces affect the activation of platelets and coagulation pathway containers depending on their surface qualities. Importantly, this could produce variability of coagulation results obtained with thrombelastographical analysis. We assessed the effects of blood storage on thrombelastograph, TEG, variables using polypropylene and polycarbonate containers. METHODS: An in vitro experiment was performed, with eight volunteers in each limb. Fresh whole blood was stored in polypropylene or polycarbonate tubes prior to TEGanalysis, to assess the role of these plastics in the TEG results obtained. RESULTS: The polycarbonate tubes displayed slower onset of coagulation and greater variability of data for all four basic TEG variables (r-time, k-time, alpha-angle and maximum amplitude, P < 0.05). Polycarbonate results fell outside manufacturer reference ranges. CONCLUSIONS: It is likely that this is due to the altered surface properties and charge effects of the containers affecting proteins and platelets differently. Caution should be used in choosing which containers are used for storage of fresh blood prior to coagulation assessment, as variable results will follow where different types of plastic containers are employed.

Blood Coagulation↗
PubMed2004

Assessment of preoperative fluid depletion using bioimpedance analysis.

BACKGROUND: Fluid depletion during the perioperative period is associated with poorer outcome. Non-invasive measurement of total body water by bioimpedance may enable preoperative fluid depletion and its influence on perioperative outcome to be assessed. METHODS: Weight and foot bioimpedance were recorded under standardized conditions in patients undergoing bowel preparation (n=43) or day surgery (n=44). Fifteen volunteers also followed standard nil-by-mouth instructions on two separate occasions to assess the variabilities of weight and bioimpedance over time. RESULTS: Body weight fell by 1.27 kg (95% CI 1.03-1.50 kg; P<0.0001) and foot bioimpedance increased by 51 ohm after bowel preparation (95% CI 36-66; P<0.0001). Weight change after the nil-by-mouth period in day-surgery patients (mean -0.22 kg, 95% CI -0.05 to -0.47 kg; P=0.07) correlated (r=-0.46; P=0.005) with an increase in bioimpedance (16 ohms, 95% CI 5-27 ohms; P=0.01). No difference between two separate bioimpedance measurements was seen in the volunteer group. CONCLUSIONS: Further work is warranted to determine if bioimpedance changes may serve as a useful indicator of perioperative fluid depletion.

Adult↗
PubMed2004

A descriptive study of the variation in baseline levels of antiendotoxin core antibodies between US and UK populations.

Low levels of naturally occurring antibodies to the core section of endotoxin (EndoCAb) have been shown to be predictors of poor outcome following major surgery. We performed a retrospective study comparing pre-operative levels in US surgical patients, UK surgical patients and healthy volunteers. Both IgM and IgG EndoCAb levels were higher in the US surgical patients when compared with the other groups (approximately twice as high in the case of IgG EndoCAb). This may reflect genetic or environmental variability between the patient groups, differences in the disease processes, the disparity in the delivery of health care between the two countries or degradation of the samples in transfer.

Antibodies, Bacterial↗
PubMed2003

Comparison of P-POSSUM risk-adjusted mortality rates after surgery between patients in the USA and the UK.

BACKGROUND: The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) criteria have been used to assess surgical risk in patients in the UK. The aim was to determine how applicable these criteria are to patients undergoing surgery in the USA. METHODS: Two cohorts of patients undergoing major non-cardiac surgery were followed prospectively in the USA (n = 1056) and the UK (n = 1539). Each patient was assigned a risk score for preoperative physiological status and operative severity using the established POSSUM criteria. Death in hospital was the primary outcome measure. For each patient a predicted risk of death was calculated from Portsmouth POSSUM (P-POSSUM) methodology using an established equation. The relationships between predicted and observed mortality rates in each cohort were investigated by means of multivariate logistic regression. RESULTS: Within each cohort, an increase in risk estimated by P-POSSUM predicted an increase in observed mortality rate (P < 0.001). For any given risk level, however, mortality rates were significantly higher in the UK cohort than in the US cohort (odds ratio 4.50 (95 per cent confidence interval 2.81 to 7.19); Z = 6.25, P < 0.001). CONCLUSION: An increase in predicted risk, based on the P-POSSUM methodology, was associated with a higher mortality rate in patients from both countries. However, risk-adjusted mortality rates following major surgery were four times higher in the UK cohort. These marked differences warrant validation in a larger number of centres.

Cohort Studies↗
PubMed2002

Coagulation effects of in vitro serial haemodilution with a balanced electrolyte hetastarch solution compared with a saline-based hetastarch solution and lactated Ringer's solution.

The hydroxyethyl starches are a group of compounds that has been associated with impairment of coagulation when large volumes are administered. The thrombelastograph is commonly used to assess point-of-care whole blood coagulation. Little is known about the dose-response relationships of haemodilution, and it is reasonable to assume that a linear association exists. This may not be the case with altered electrolyte compositions of the fluids used for haemodilution. We have therefore conducted an in vitro study of haemodilution of human whole blood using lactated Ringer's solution and two high molecular weight hetastarches, one in a balanced salt solution, the other in a 0.9% saline solution. The thrombelastograph, commonly used for the assessment of the coagulation effects of synthetic colloids, was used as the coagulation assessment device. Serial haemodilution with hetastarch in a balanced salt solution demonstrated a biphasic response (of r-times and k-times, as well as alpha angles), with haemodilution in the 20-40% range causing enhanced coagulation, and higher degrees of dilution causing a decrease in overall coagulation performance. A similar picture was observed with lactated Ringer's solution, but only significantly so in alpha angles. Hetastarch in saline did not display this initial increased coagulability at mild to moderate dilutions. This biphasic response of lactated Ringer's solution and hetastarch in a balanced salt solution reflects the complex interaction of fluids and the coagulation system, and that these effects cannot be attributed to simple haemodilution. On the other hand, there was a linear decrease in maximum amplitude with haemodilution. Maximum amplitude was particularly affected by both starches, which is an expected finding in view of the known interaction between the hydroxyethyl starches and von Willebrand's factor.

Blood Coagulation↗
PubMed2002

The effect of hypothermia on calculated values using saline and automated air tonometry.

OBJECTIVE: To quantify in vitro the effect of hypothermia on results obtained when performing automated air tonometry (Tonocap, Datex-Ohmeda, Instrumentarium Corp, Helsinki, Finland) and saline tonometry. DESIGN: In vitro validation study. SETTING: University hospital research laboratory. INTERVENTIONS: Two TRIP sigmoid catheters, one connected to the Tonocap device and the other instilled with 2.5 mL of 0.9% saline, were placed in a saline bath at 30.3 degrees C (mean) through which 5% carbon dioxide (CO(2)) was bubbled. MEASUREMENTS AND MAIN RESULTS: A total of 50 paired measurements were taken at 30-minute equilibration times of saline bath CO(2) tension and saline tonometry and air tonometry readings. Saline samples were analyzed at 37 degrees C and corrected for temperature. Bias and precision of each technique as a percentage of predicted CO(2) values were calculated. The Tonocap device had bias and precision values of -2.6% and +/-1.4%. Measurement of CO(2) is in the gaseous phase so that temperature correction is not required. Saline tonometry readings processed at 37 degrees C exhibited a large positive bias of 23.06% (precision +/- 7.02%). Correction for temperature improved bias to -10.98 % with a similar precision profile of +/-5.78%. CONCLUSION: When using gastrointestinal tonometry during hypothermic cardiopulmonary bypass, saline tonometry samples should be temperature corrected. The Tonocap device proved the most accurate and precise measurement technique independent of the need for temperature correction.

Carbon Dioxide↗
PubMed2002

A prospective, randomized comparison of thromboelastographic coagulation profile in patients receiving lactated Ringer's solution, 6% hetastarch in a balanced-saline vehicle, or 6% hetastarch in saline during major surgery.

OBJECTIVES: To compare the effects of lactated Ringer's solution (LR), 6% hetastarch in a balanced-saline vehicle (HS-BS), and 6% hetastarch in normal saline (HS-NS) on coagulation using thromboelastography. DESIGN: Prospective, randomized double-blinded evaluation of previously published clinical trial. SETTING: Tertiary-care medical center. PARTICIPANTS: Patients undergoing elective noncardiac surgery with an anticipated blood loss >500 mL. A total of 90 patients were enrolled with 30 patients in each group. INTERVENTIONS: Patients received a standardized anesthetic. LR, HS-BS, and HS-NS were administered intraoperatively based on a fluid administration algorithm. Hemodynamic targets included maintenance of arterial blood pressure, heart rate, and urine output within a predefined range. MEASUREMENTS AND MAIN RESULTS: Thromboelastography variables for r time, k time, maximum amplitude, and alpha angle (mean +/- SD) were recorded at induction of anesthesia, at the end of surgery, and 24 hours postoperatively. Patients in the LR group showed a state of hypercoagulation at the end of surgery with reductions (p < 0.005) in r time (-3.8 +/- 6.7 mm) and k time (-1.7 +/- 2.5 mm). This state of hypercoagulation continued into the postoperative period. Patients in the HS-NS group showed a state of hypocoagulation with increases (p < 0.05) in r time (+6.2 +/- 8.5 mm) and k time (+1.7 +/- 3.9 mm) and a reduction in maximum amplitude (-8.0 +/- 9.8 mm) at the end of surgery. This state of hypocoagulation was reduced in the postoperative period. Patients in the HS-BS group showed no significant changes in coagulation status at end of surgery, with the smallest changes in r time (-0.3 +/- 4.1 mm), k time (+0.1 +/- 3.1 mm), maximum amplitude (-5.4 +/- 12.3 mm), and alpha angle (0.3 +/- 12.5 degrees ). CONCLUSION: LR-treated patients exhibited a hypercoagulative profile that persisted into the postoperative period. HS-BS administration was associated with a lesser change in the coagulation profile compared with HS-NS, which was associated with a hypocoagulative state.

Aged↗
PubMed2001

Preoperative and intraoperative predictors of postoperative morbidity, poor graft function, and early rejection in 190 patients undergoing liver transplantation.

HYPOTHESIS: Preoperative and intraoperative variables predict in part adverse outcome after liver transplantation. DESIGN: Prospective, blinded, cohort study. SETTING: Tertiary care hospital. SUBJECTS: A total of 190 adult patients undergoing primary liver transplantation. MAIN OUTCOME MEASURE: Adverse outcome was prospectively defined as either in-hospital death or prolonged postoperative hospitalization (>14 days) associated with morbidity. Potential preoperative and intraoperative risk factors were collected. Associations were tested by univariate analysis followed by multivariate analysis in which preoperative factors were entered before intraoperative factors. RESULTS: Adverse outcome occurred in 44.7% of patients. Incidences of other complications were as follows: in-hospital mortality (8.4%), primary graft nonfunction (4.2%), poor early graft function (1.1%), and early rejection (31.2%). Univariate predictors of adverse outcome were United Network for Organ Sharing status (P =.003), Child-Turcotte-Pugh score (P =.02), POSSUM physiological score (P =.002), recipient age (P =.01), preoperative serum high-density lipoprotein cholesterol level (P =.03), preoperative serum creatinine level (P =.002), preoperative serum total IgG level (P =.004), duration in hospital preoperatively (P =.03), operative duration (P<.001), allogeneic erythrocyte transfusions (P<.001), total intraoperative fluids (P =.002), and use of inotropic agents (P =.01). In the final multivariate model, predictors of adverse outcome were United Network for Organ Sharing status (P =.03), recipient age (P =.002), and total intraoperative fluids (P =.04). Most patients who died or had a prolonged hospitalization exhibited dysfunction of more than 1 organ system, including pulmonary, renal, and infectious complications. CONCLUSIONS: Adverse outcome occurs frequently after liver transplantation, usually involves multiple organ systems, and is predicted in part by several preoperative and intraoperative factors.

Cholesterol, HDL↗
PubMed2001

Endotoxin-neutralizing capacity of serum from cardiac surgical patients.

OBJECTIVE: To determine if endotoxin core antibody (EndoCAb) from the serum of cardiac surgical patients neutralizes endotoxin in an ex vivo biologic assay. DESIGN: Prospective blinded cohort study. SETTING: Academic medical center. PARTICIPANTS: Patients (n = 203) undergoing cardiac surgery. INTERVENTIONS: Sera were obtained from patients preoperatively. MEASUREMENTS AND MAIN RESULTS: EndoCAb levels were determined by enzyme-linked immunosorbent assay. Sera were incubated for 15 minutes at 37 degrees C with varying concentrations of endotoxin from a clinically relevant bacterium (Escherichia coli serotype O18), then tested for the presence of endotoxin activity using the validated Limulus amebocyte lysate assay. Median (interquartile range) IgM and IgG EndoCAb levels were 118 median units (range, 31 to 259 median units) and 208 median units (range, 108 to 401 medium units). Increasing levels of IgM EndoCAb were associated with increased neutralization of endotoxin (p < 0.0001). Increasing levels of IgG EndoCAb were associated with increased neutralization of endotoxin (p < 0.0001). An additive effect of IgM and IgG EndoCAb levels on endotoxin neutralization was observed without evidence of synergistic or plateau effects. EndoCAb levels did not completely predict serum neutralization capacity. CONCLUSION: Anti-EndoCAbs of both classes (IgM and IgG) were able to neutralize lipopolysaccharide from a clinically relevant bacterium in an ex vivo model. Neither Igm nor IgG appeared to be more capable of neutralization in this model. These antibodies did not completely predict neutralization capacity; other endogenous factors in human serum must be capable of lipopolysaccharide neutralization.

Antibodies, Bacterial↗
PubMed2001

The effects of balanced versus saline-based hetastarch and crystalloid solutions on acid-base and electrolyte status and gastric mucosal perfusion in elderly surgical patients.

UNLABELLED: The IV administration of sodium chloride solutions may produce a metabolic acidosis and gastrointestinal dysfunction. We designed this trial to determine whether, in elderly surgical patients, crystalloid and colloid solutions with a more physiologically balanced electrolyte formulation, such as Hartmann's solution and Hextend, can provide a superior metabolic environment and improved indices of organ perfusion when compared with saline-based fluids. Forty-seven elderly patients undergoing major surgery were randomly allocated to one of two study groups. Patients in the Balanced Fluid group received an intraoperative fluid regimen that consisted of Hartmann's solution and 6% hetastarch in balanced electrolyte and glucose injection (Hextend). Patients in the Saline group were given 0.9% sodium chloride solution and 6% hetastarch in 0.9% sodium chloride solution (Hespan). Biochemical indices and acid-base balance were determined. Gastric tonometry was used as a reflection of splanchnic perfusion. Postoperative chloride levels demonstrated a larger increase in the Saline group than the Balanced Fluid group (9.8 vs 3.3 mmol/L, P = 0.0001). Postoperative standard base excess showed a larger decline in the Saline group than the Balanced Fluid group (-5.5 vs -0.9 mmol/L, P = 0.0001). Two-thirds of patients in the Saline group, but none in the Balanced Fluid group, developed postoperative hyperchloremic metabolic acidosis (P = 0.0001). Gastric tonometry indicated a larger increase in the CO2 gap during surgery in the Saline group compared with the Balanced Fluid group (1.7 vs 0.9 kPa, P = 0.0394). In this study, the use of balanced crystalloid and colloid solutions in elderly surgical patients prevented the development of hyperchloremic metabolic acidosis and resulted in improved gastric mucosal perfusion when compared with saline-based solutions. IMPLICATIONS: This prospective, randomized, blinded trial showed that, in elderly surgical patients, the use of balanced IV solutions can prevent the development of hyperchloremic metabolic acidosis and provide better gastric mucosal perfusion compared with saline-based fluids.

Acid-Base Equilibrium↗
PubMed2001

Decreased endotoxin immunity is associated with greater mortality and/or prolonged hospitalization after surgery.

BACKGROUND: Patients undergoing noncardiac surgery often develop postoperative morbidity, potentially attributable to endotoxemia and the systemic inflammatory response syndrome. Endogenous antibodies to endotoxin may confer protection from endotoxin-mediated toxicity. The authors sought to determine the association of preoperative antiendotoxin immunity and death or prolonged hospitalization in a broad population of general surgical patients undergoing major surgery. METHODS: To test the hypothesis that low preoperative serum antiendotoxin core antibody (EndoCAb) concentration is an independent predictor of adverse outcome after general surgery, 1,056 patients undergoing routine noncardiac surgery were enrolled into a prospective, blinded, cohort study. Immunoglobulin M EndoCAb, immunoglobulin G EndoCAb, total inmunoglobulin M, and immunoglobulin G concentrations were measured in serum obtained preoperatively. A physiologic risk score using the established POSSUM criteria was assigned preoperatively to each patient. The primary predefined composite end point (postoperative complication) was either in-hospital death or postoperative length of stay greater than 10 days. Multivariate logistic regression was used to test the study hypothesis. RESULTS: Overall, postoperative complication occurred in 234 of the 1,056 patients (22.1%). Lower immunoglobulin M EndoCAb concentration (P = 0.006) predicted increased risk of postoperative complication independent of POSSUM physiologic risk score (P < 0.001). In contrast, total immunoglobulin M and total immunoglobulin G concentrations did not predict adverse outcome. Complications involved multiple organ systems and were generally unrelated to the type or site of surgery, consistent with the systemic inflammatory response syndrome. CONCLUSIONS: Adverse outcome after routine noncardiac surgery is common and is predicted in part by low concentrations of EndoCAb. The authors' findings suggest that endotoxemia may be a cause of postoperative morbidity after routine noncardiac surgery.

Adult↗
PubMed2001

Gastric tonometry: where do we stand?

Gastric tonometry has proved to be a sensitive but not specific predictor of outcome in the critically ill. The data accumulated to date indicate that those patients able to achieve or maintain a normal gastric mucosal pH do better than those who do not. In addition, therapy aimed at improving an abnormal gastric mucosal pH has proved to be less successful. These findings may simply indicate that tonometry identifies those "responders" and "nonresponders," as becomes increasingly apparent in populations of critical care patients receiving interventional therapy. Gastric tonometry has undergone a number of methodologic changes over the last decade, seeing a switch from saline to automated gas tonometry. Along with this switch of methodology has come a deeper scrutiny of the indices used to assess gut perfusion. Most studies (including all the interventional ones) have used gastric mucosal pH. The newer indices of gut luminal PCO2 (PgCO2) referenced to arterial CO2 (PgCO2-PaCO2) or end tidal CO2 (PgCO2-PeCO2), although relatively well validated, remain to be proven as predictors of outcome or guides to interventional therapy. If we take a fresh look at the interventional trials in intensive care patients, there is a very definite trend toward benefit in the protocol groups, although they are generally reported as negative studies. There is much to be accomplished, however, before we accept the gastric tonometer as a routine tool with which to guide therapy based on gastrointestinal perfusion, including a greater understanding of gastrointestinal physiology and, as ever, the call for an adequately powered prospective randomized controlled trial to evaluate the clinical utility of gas tonometry.

Carbon Dioxide↗
PubMed2000

Understanding gastrointestinal perfusion in critical care: so near, and yet so far.

An association between abnormal gastrointestinal perfusion and critical illness has been suggested for a number of years. Much of the data to support this idea comes from studies using gastric tonometry. Although an attractive technology, the interpretation of tonometry data is complex. Furthermore, current understanding of the physiology of gastrointestinal perfusion in health and disease is incomplete. This review considers critically the striking clinical data and basic physiological investigations that support a key role for gastrointestinal hypoperfusion in initiating and/or perpetuating critical disease.

Blood Gas Analysis↗