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M G Mythen

Publications and source records attributed to M G Mythen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Report from the meeting: Gastrointestinal Tonometry: State of the Art. 22nd-23rd May 1998, London, UK.

Gastrointestinal (GI) tonometry, the only clinically available method for the accurate diagnosis of compromised GI blood flow, has been shown to be a sensitive predictor of increased morbidity, mortality and prolonged hospitalization. The recent introduction of the Tonocap, as a means of performing automated air tonometry, has simplified the application of GI tonometry in the clinical setting. Despite this the utility of GI tonometry remains controversial. The GI Tonometry: State of the Art meeting brought together a group of clinicians with a proven track record of research, clinical interest and expertise in this field. The aim of the meeting was to come to a consensus regarding certain issues such as the past and future roles of GI tonometry and standards for its correct usage and interpretation. Finally suggestions as to further research and clinical evaluation were made within a broader discussion regarding the complexities of applying the principles of evidence-based medicine to the introduction of a new piece of medical technology.

Carbon Dioxide↗
PubMed2000

Automated detection of gastric luminal partial pressure of carbon dioxide during cardiovascular surgery using the Tonocap.

BACKGROUND: A new automated system of air tonometry (Tonocap; Datex Ohmeda, Helsinki, Finland) allows for frequent (every 15 min) measurement of gastric luminal partial pressure of carbon dioxide. Its use has not been described in cardiac surgical patients. METHODS: One hundred patients undergoing coronary artery bypass graft or cardiac valve surgery were enrolled in a prospective cohort study. After anesthetic induction and insertion of a TRIP NGS Catheter (Datex Ohmeda), measurements of gastric luminal partial pressure of carbon dioxide were obtained using the Tonocap, and gastric mucosal pH (pHi) was calculated. The main outcome measure was postoperative complication, defined as either in-hospital death or prolonged postoperative hospitalization (> 14 days). RESULTS: Four patients (4%) died, all of multiple-system organ failure, one each on postoperative days 9, 26, 46, and 121. Postoperative complication occurred in 18 patients (18%), all of whom exhibited persistent dysfunction of at least one organ system. Perioperatively, an abnormal pHi (< 7.32) and gastric luminal minus arterial partial pressure of carbon dioxide gap (> 8 mmHg) occurred in 66% and 70% of patients, respectively. Predictors of postoperative complication included postoperative pHi (P = 0.001), gastric luminal partial pressure of carbon dioxide (P = 0.022), and gastric luminal minus arterial partial pressure of carbon dioxide gap (P = 0.013). In contrast, arterial base excess (P > 0.4) and routinely measured hemodynamic variables (e.g., heart rate, blood pressure) were either less predictive compared with Tonocap-derived variables or not predictive. CONCLUSIONS: Despite a low mortality rate, patients undergoing cardiac surgery exhibited high incidences of prolonged hospitalization and postoperative morbidity. The Tonocap was easy to use, particularly compared with saline tonometry. Several Tonocap-derived variables were predictive of postoperative complications consistent with previously published data using saline tonometry.

Aged↗
PubMed2000

Comparison of the response of saline tonometry and an automated gas tonometry device to a change in CO2.

OBJECTIVE: To examine the speed of response of saline tonometry and an automated gas tonometry system by using standard tonometry catheters. DESIGN: In vitro validation study. SETTING: Experimental research laboratory. INTERVENTIONS: Tonometry catheters were placed in a test chamber designed to simulate the lumen of a hollow viscus and were exposed to a rapid change in CO2 from 0% to 5% or 10%. Measured CO2 over time was fit to a mathematical model to determine the response time constant (the time to reach 63% of the final value) for each system. MEASUREMENTS AND MAIN RESULTS: Response time to a change in CO2 was significantly faster with the automated gas system than with traditional saline tonometry. The mathematical time constant for a 5% change in CO2 in a gas environment was 2.8 mins (95% confidence interval, 2.6-3.0 mins) for the gas and 6.3 mins (95% confidence interval, 5.8-7.3 mins) for the saline technique. These times were longer for the CO2 change in a liquid environment: The time constant was 4.6 mins (95% confidence interval, 4.5-4.7 mins) for the gas system and 7.8 mins (95% confidence interval, 7.15-8.6 mins) for the saline tonometry. There was a significantly lower final equilibration value for the CO2 measurement with saline tonometry. There was essentially no difference in time constants for each system for a 5% change compared with a 10% CO2 change, except for a slightly faster time constant for the gas tonometry system with a 5% change in the gas environment (5%: 2.8 mins vs. 10%: 3.3 mins). CONCLUSIONS: The automated gas tonometry system has a significantly faster response to a change in CO2 than conventional saline tonometry.

Carbon Dioxide↗
PubMed2000

Preparation and preclinical evaluation of a novel liposomal complete-core lipopolysaccharide vaccine.

Our objective is to develop a prophylactic vaccine strategy that can be evaluated for surgical and other high-risk hospitalized patients. In this paper, we describe the preparation and preclinical evaluation of a liposomal complete-core lipopolysaccharide (LPS) vaccine that is nontoxic and broadly antigenic. Complete-core (Ra-chemotype) LPSs were isolated from four gram-negative bacterial strains (Escherichia coli K-12, E. coli R1, Pseudomonas aeruginosa PAC608, and Bacteroides fragilis), mixed together to form a cocktail of complete-core LPSs, and then incorporated into multilamellar liposomes consisting of dimyristoyl phosphatidyl choline, dimyristoyl phosphatidylglycerol, and cholesterol in a 4:1:4 molar ratio. The endotoxic activities of these LPS-containing liposomes were less than 0.1% of the endotoxicities of the original free LPSs as measured by the Limulus amoebocyte lysate assay. In vivo administration of liposomal complete-core LPS mixed with Al(OH)(3) to rabbits resulted in no pyrogenicity or overt toxicity over a 7-day period. In immunoblots, sera from rabbits following active immunization elicited cross-reactive antibodies to a large panel of rough and smooth LPSs from numerous clinically relevant gram-negative bacteria, including E. coli (serotypes O1, O4, O6, O8, O12, O15, O18, O75, O86, O157, and O111), P. aeruginosa (Fisher-Devlin serotypes 1, 2, and 3, which correspond to International Antigenic Typing Scheme types 6, 11, and 2, respectively), Klebsiella pneumoniae (serotypes O1, O2ab, and O3), B. fragilis, and Bacteroides vulgatus. Active immunization of mice with liposomal complete-core LPS provided protection against a lethal challenge with E. coli O18 LPS. The vaccine tested was nontoxic, nonpyrogenic, and immunogenic against a wide variety of pathogens found in clinical settings.

Animals↗
PubMed1999

Hextend, a physiologically balanced plasma expander for large volume use in major surgery: a randomized phase III clinical trial. Hextend Study Group.

UNLABELLED: Hextend (BioTime, Inc., Berkeley, CA) is a new plasma volume expander containing 6% hetastarch, balanced electrolytes, a lactate buffer, and physiological levels of glucose. In preclinical studies, its use in shock models was associated with an improvement in outcome compared with alternatives, such as albumin or 6% hetastarch in saline. In a prospective, randomized, two-center study (n = 120), we compared the efficacy and safety of Hextend versus 6% hetastarch in saline (HES) for the treatment of hypovolemia during major surgery. Patients at one center had a blood sample drawn at the beginning and the end of surgery for thromboelastographic (TEG) analysis. Hextend was as effective as HES for the treatment of hypovolemia. Patients received an average of 1596 mL of Hextend: 42% received >20 mL/kg up to a total of 5000 mL. No patient received albumin. Hextend-treated patients required less intraoperative calcium (4 vs 220 mg; P < 0.05). In a subset analysis of patients receiving red blood cell transfusions (n = 56; 47%), Hextend-treated patients had a lower mean estimated blood loss (956 mL less; P = 0.02) and were less likely to receive calcium supplementation (P = 0.04). Patients receiving HES demonstrated significant prolongation of time to onset of clot formation (based on TEG) not seen in the Hextend patients (P < 0.05). No Hextend patient experienced a related serious adverse event, and there was no difference in the total number of adverse events between the two groups. The results of this study demonstrate that Hextend, with its novel buffered, balanced electrolyte formulation, is as effective as 6% hetastarch in saline for the treatment of hypovolemia and may be a safe alternative even when used in volumes up to 5 L. IMPLICATIONS: Hextend (BioTime, Inc., Berkeley, CA) is a new plasma volume expander containing 6% hetastarch, balanced electrolytes, a lactate buffer, and a physiological level of glucose. It is as effective as 6% hetastarch in saline for the treatment of hypovolemia but has a more favorable side effects profile in volumes of up to 5 L compared with 6% hetastarch in saline.

Adult↗
PubMed1999

The use of a postoperative morbidity survey to evaluate patients with prolonged hospitalization after routine, moderate-risk, elective surgery.

UNLABELLED: Vital healthcare resources are devoted to caring for patients with prolonged hospitalization after routine, moderate-risk surgery. Despite the significant cost, little is known about the overall incidence and pattern of complications in these patients. Four hundred thirty-eight patients undergoing a diverse group of routine, moderate-risk, elective surgical procedures were enrolled into a prospective, blinded, cohort study. Complications were assessed using a postoperative morbidity survey. The main outcome was postoperative complication, defined as either in-hospital death or prolonged postoperative hospitalization (> 7 days). The mortality rate was 1.6%. Postoperative complications occurred in 118 patients (27% [95% CI 23-31]). Complications frequently observed in these patients included: gastrointestinal 51% (42-60), pulmonary 25% (17-33), renal 21% (14-28), and infectious 13% (7-19). Most complications were not directly related to the type/site of surgery. Indices of tissue trauma (blood loss [P < 0.001], surgical duration [P = 0.001]) and tissue perfusion (arterial base deficit [P = 0.008], gastric pHi [P = 0.02]) were the strongest intraoperative predictors of complications. Despite a low mortality rate, we found that complications after routine, moderate-risk, elective surgery are common and involve multiple organ systems. Our 9-point survey can be used by healthcare providers and payers to characterize post-operative morbidity in their respective settings. IMPLICATIONS: Little is known about the overall incidence and pattern of complications in patients with prolonged hospitalization after routine, elective surgery. We prospectively assessed these complications using a novel postoperative morbidity survey. The postoperative morbidity survey can be used in future clinical outcome trials, as well as in routine hospital-based quality assurance.

Data Collection↗
PubMed1998

Gastric mucosal tonometry: towards new methods and applications.

Gastrointestinal tonometry is a minimally-invasive method of assessing splanchnic perfusion. The measurement of regional-CO2 (PrCO2) and calculation of intra-mucosal pH (pHi) using the gastro-intestinal tonometer has been shown to be predictive of outcome in critically ill patients. Furthermore, the use of tonometrically derived data as therapeutic indices have been associated with improved outcome. The original balloon-saline method of tonometry was laborious, cumbersome and prone to systematic errors. The Tonocap (Tonometrics Division Instrumentarium Corp., Datex, Finland) is an automated on-line air based system. We present here a detailed description of the Tonocap along with a summary of the results of some of the original in-vitro, animal in-vivo and human experiments. The Tonocap is a major advance in regional monitoring and its introduction into clinical practice should allow widespread assessment of the value of gastro--intestinal tonometry in the management of the critically ill.

Animals↗
PubMed1998

Effect of alpha(alpha)-cross-linked hemoglobin and pyridoxalated hemoglobin polyoxyethylene conjugate solutions on gastrointestinal regional perfusion in hemorrhagic shock.

BACKGROUND: Hemoglobin-based blood substitutes may cause vasoconstriction, which could limit organ perfusion during trauma resuscitation. We investigated the effect of two hemoglobin solutions on regional blood flow and mucosal perfusion in the gastrointestinal tract in a hemorrhagic shock model. METHODS: Twenty-four swine were bled 30% of blood volume over 1 hour. Six additional animals were anesthetized and monitored but did not undergo hemorrhage. Bled animals were resuscitated with alpha(alpha)-hemoglobin (alpha(alpha)Hb), pyridoxalated hemoglobin polyoxyethylene conjugate (PHP), shed blood, or lactated Ringer's solution. Regional blood flow was measured by radiolabeled microspheres. Gastric mucosal perfusion was estimated by measuring intramucosal pH (pHi) by tonometry. RESULTS: PHP and shed blood restored small-bowel flows to sham values, whereas lactated Ringer's solution and alpha(alpha)Hb did not. Shed blood and PHP, but not alpha(alpha)Hb, restored cardiac index (CI) to baseline (p < 0.05). Mean pulmonary artery pressure was elevated over baseline with alpha(alpha)Hb and PHP and remained elevated with alpha(alpha)Hb (p < 0.05). pHi was significantly lower after resuscitation with PHP than with other fluids. CONCLUSION: PHP was efficacious in restoring CI and small-bowel flow, but the pHi remained low, indicating possible continued mucosal ischemia. Alpha(alpha)Hb led to limited recovery of CI and small-bowel blood flow but restored pHi close to baseline. Shed blood was efficacious in restoration of pHi, gastrointestinal blood flows, and systemic hemodynamics.

Animals↗
PubMed1997

Relationship of preoperative antiendotoxin core antibodies and adverse outcomes following cardiac surgery.

OBJECTIVE: To test the hypothesis that low serum antiendotoxin core antibody (EndoCAb) level is an independent predictor of adverse outcome following cardiac surgery. DESIGN: Prospective, blinded, cohort study. SETTING: Tertiary care medical center. SUBJECTS: A total of 301 patients undergoing coronary artery bypass graft surgery and/or valvular heart surgery. DESIGN: Preoperative serum was assayed for IgM EndoCAb, IgG EndoCAb, total IgM, and total IgG levels. Known preoperative risk factors were assessed, and patients were assigned a risk score using a validated method. MAIN OUTCOME MEASURE: A major complication, defined as either in-hospital death or postoperative length of stay greater than 10 days. RESULTS: Overall, a major complication occurred in 34 patients (11.3%). Lower IgM EndoCAb level independently predicted (P=.002) increased risk of major complication over and above the effects of preoperative risk score (P=.02), total IgG level (P=.07), and all other known perioperative risk factors. In contrast, IgG Endo-CAb and total IgM concentrations did not predict outcome. No association existed between risk score and level of IgM EndoCAb. CONCLUSION: There is marked preoperative variability in humoral immunity against endotoxin core, which is not accounted for by differences in known preoperative risk factors. In this study, low levels of IgMEndoCAb were an important independent predictor of adverse postoperative outcome, which supports the theory that endotoxemia is a cause of postoperative morbidity.

Aged↗
PubMed1997

Measurement of gastrointestinal intramucosal pH is a poor guide to tolerable levels of anemia during isovolemic hemodilution in a canine model of coronary stenosis.

OBJECTIVE: To determine the relationship between gastrointestinal intramucosal pH and myocardial oxygenation during isovolemic hemodilution in dogs with critical coronary artery stenoses. DESIGN: Prospective sequential evaluation of ileal intramucosal pH and regional myocardial function of a critically perfused area of myocardial tissue in a canine model of normovolemic hemodilution. SETTING: A research laboratory. SUBJECTS: Fifteen dogs. INTERVENTIONS: A micrometer snare was placed around a main coronary artery (8 left anterior descending artery, 7 right coronary artery). Three pairs of sonomicrometer crystals were placed in the heart to measure regional myocardial contraction. A gastrointestinal tonometer was placed in the ileum and used to measure luminal PCO2. This PCO2 value was used to calculate the ileal intramucosal pH. The animals underwent normovolemic hemodilution until myocardial ischemia occurred in the region supplied by the snared vessel. Measurements were continued for a further 40 minutes. MEASUREMENTS AND MAIN RESULTS: Following instrumentation, stabilization, and critical constriction of a coronary vessel, percentage changes in systolic shortening of myocardial tissue in the region of critical perfusion were determined every 20 minutes. Ileal intramucosal pH and commonly measured cardiovascular variables were determined at the same time points. Myocardial ischemia occurred after 80 minutes of hemodilution, when the mean (+/- SD) hemoglobin concentration had fallen from a baseline level of 123 +/- 18 g/L to 82 +/- 14 g/L (P < .01). From the start of hemodilution to 40 minutes after myocardial ischemia occurred, there were no significant changes in heart rate, cardiac output, oxygen consumption, arterial acid-base balance, or arterial PCO2. Oxygen delivery decreased by approximately 45% (5.99 +/- 1.66 to 3.41 +/- 0.90 mL/kg per minute; P < .01) but there were no changes in ileal intramucosal pH (7.31 +/- 0.08 to 7.30 +/- 0.08; P = .90). CONCLUSIONS: Myocardium compromised by coronary stenosis is more sensitive to normovolemic hemodilution-induced ischemia than the normally perfused gut mucosa. This limits the potential utilization of the measurement of gastrointestinal intramucosal pH as a guide to tolerable levels of anemia in critically ill patients.

Anemia↗
PubMed1997

Comparison of commonly used clinical indicators of hypovolaemia with gastrointestinal tonometry.

OBJECTIVE: The gastrointestinal tonometer, which allows measurement of gastrointestinal mucosal CO2 and subsequent derivation of gut intramucosal pH (pHi), has been demonstrated to be a sensitive predictor of outcome following major surgery. Current theory suggests that the origin of the low pH may be hypovolaemia. This study was designed to compare the temporal sequence of changes in tonometric readings with invasive blood pressure, stroke volume, heart rate, lactate and arterial blood gas measurements during progressive haemorrhage. DESIGN: Observational healthy volunteer study. SETTING: Intensive care unit at University College London Hospitals. SUBJECTS: Six healthy, medically qualified volunteers. INTERVENTIONS: After obtaining baseline measurements, the subjects were progressively bled 25% (range = 21-31%) of their blood volume over a period of 1 h in two approximately equal aliquots. Equilibration was allowed for 30 min following the bleed, after which further measurements were made and the blood was then retransfused over 30 min. MEASUREMENTS AND MAIN RESULTS: There was no consistent change in any of the haemodynamic variables other than gastric intramucosal CO2:arterial CO2 gap (PiCO2-PaCO2) after removal of the first aliquot of blood, although five of the six subjects also demonstrated a fall in pHi. After removal of the second aliquot of blood, PiCO2-PaCO2 gap and pHi continued to indicate a worsening gastric intramucosal acidosis; stroke volume, as measured by suprasternal Doppler, demonstrated a marked fall, while all other variables measured had not altered consistently or to such a degree as to elicit a clinical response or cause suspicion of a hypovolaemic state. On retransfusion, all variables returned towards baseline. CONCLUSIONS: This study demonstrates the value of tonometry as an early monitor of hypovolaemia and highlights the shortcomings of other more commonly measured clinical variables.

Adult↗
PubMed1997

Effect of temperature during cardiopulmonary bypass on gastric mucosal perfusion.

The purpose of our study was to prospectively study the splanchnic response to hypothermic and tepid cardiopulmonary bypass (CPB) using alphastat management of arterial blood-gas tensions. Twenty-four patients for elective CABG surgery were allocated randomly to tepid (35-36 degrees C) or hypothermic (30 degrees C) bypass groups. Measurements were made at four times: (1) baseline, (2) stable during CPB (inflow temperature = nasopharyngeal temperature) 30 degrees C for hypothermic patients, bypass +20 min for tepid patients, (3) 10 min before the end of bypass, (4) after bypass, skin closure. Both groups demonstrated a significant reduction in gastric intramucosal pH (pHim) from time 1 to time 4 and there was no difference in the incidence of a low pHim between the tepid and cold groups (4/12 vs 3/12; ns) at time 4. pHim was significantly lower in the tepid groups at time 3 (P = 0.03) but this discrepancy may have been because of an artefactually high pHim in the cold group. There was a significantly higher incidence of postoperative non-cardiac complications in patients who had a low pHim at time 4 (P = 0.0008). Therefore, we conclude that although the temperature during CPB had a transient effect on pHim it is unlikely to be a major determinant in the pathogenesis of gut mucosal hypoperfusion after bypass.

Adult↗