PubMed Health⌕ Search

Biomedical subjects

B Mets

Publications and source records attributed to B Mets.

At least 19 recordsLinked to original sources

Endotoxaemia during left ventricular assist device insertion: relationship between risk factors and outcome.

BACKGROUND: Endotoxaemia, caused by splanchnic ischaemia during surgery, is believed to trigger systemic inflammation and cause postoperative organ dysfunction. A relationship between the plasma concentration of endotoxin during surgery and known risk factors for postoperative morbidity and mortality (e.g. age, abnormal gastric tonometric variables) and adverse outcome after surgery has not been demonstrated. METHODS: In a prospective study, the plasma concentration of endotoxin was measured in 12 patients undergoing implantation of a left ventricular assist device. Automated air gastric tonometry was performed in all patients. The relationship between plasma endotoxin concentration, risk factors, and postoperative outcome was explored. RESULTS: Carbon dioxide gap increased from 0.7 (0.3) to 3.6 (1.6) kPa at the end of surgery. Endotoxin was detected in one of 12 patients at baseline and in nine of 12 patients at the end of surgery (P=0.003). A high plasma concentration of endotoxin at the end of surgery was associated with a higher carbon dioxide gap (r=0.59, P<0.05), and a higher postoperative multiple organ dysfunction score (r=0.7, P=0.01). CONCLUSIONS: The finding of an association between high intraoperative plasma concentrations of endotoxin, abnormal gastric tonometric variables and adverse outcome supports the view that endotoxaemia is caused by gut hypoperfusion during surgery and is associated with postoperative organ dysfunction.

Adult↗

Validation of continuous thermodilution cardiac output in patients implanted with a left ventricular assist device.

OBJECTIVE: To assess the accuracy of a continuous cardiac output (CCO) monitor against an independent, intravascular measurement of flow as can be performed in patients fitted with a left ventricular assist device (LVAD). DESIGN: A prospective cohort study. SETTING: Academic tertiary-care center. PARTICIPANTS: Adult patients (n = 15) presenting for LVAD placement. INTERVENTIONS: Consenting patients presenting for LVAD placement for end-stage cardiac failure were anesthetized, and a CCO pulmonary artery catheter was placed (OptiQ, CCO/SvO(2); Abbott Critical Care, North Chicago, IL). Patients were monitored with transesophageal echocardiography and excluded from analysis if aortic regurgitation was found. Cardiac output was determined using a Q-Vue, CCO/SvO(2) computer with digital readout (Abbott Critical Care, North Chicago, IL). The LVAD was placed in standard fashion during cardiopulmonary bypass. The Thoratec vented electric Heartmate (Thoratec Co, Pleasanton, CA) incorporates an LVAD flow console, which computes LVAD flow within +/- 5% (range, 1.8 to 10 L/min). MEASUREMENTS AND MAIN RESULTS: Cardiac output flow measurements were made from both systems at the following time points: 5 minutes and 30 minutes after protamine administration, at chest closure, and after skin closure. Mean cardiac output for each device did not differ at any time point. Regression analysis (Pearson's) showed acceptable correlation (r(2) = 0.79, p < 0.0001), whereas a bias of 529 mL with limits of agreement of 1,208 mL were shown for CCO measurement compared with LVAD flow. CONCLUSION: The data indicate that the CCO system tends to overestimate cardiac output by approximately 500 mL/min when compared with LVAD flow. Nevertheless, this bias is within the range found by other less-invasive studies done to assess the accuracy of this system and further serves to confirm its relative accuracy.

Cardiac Output↗

Unsuspected concentric tracheal rings in a 14-year-old with scoliosis.

A 14-yr-old boy was first found to have tracheal stenosis when anaesthesia was induced for extensive scoliosis surgery in the prone position. There are no guidelines for airway management under these conditions. We describe how we managed the problem and suggest some useful modifications.

Adolescent↗

The impact of newly diagnosed patent foramen ovale in patients undergoing off-pump coronary artery bypass grafting: case series of eleven patients.

UNLABELLED: The increased use of transesophageal echocardiography (TEE) by anesthesiologists may lead to an increase in the intraoperative detection of previously undiagnosed patent foramen ovale (PFO). The impact of heart manipulation on interatrial shunting through a PFO during off-pump coronary artery bypass graft (CABG) has not been studied. We retrospectively studied 11 patients with PFOs who underwent off-pump CABG. TEE contrast studies and blood gas analyses were performed at baseline, during heart elevation for distal coronary arteries anastomoses, and at the end of the surgery. At baseline, 5 of 11 patients had left-to-right shunting and 2 of 11 had right-to-left shunting. Heart elevation did not result in oxygen desaturation in any patient; however, it caused the disappearance of a right-to-left shunt (n = 1), persistence of this shunt (n = 1), and the development of a new right-to-left shunt (n = 2). Return of the heart to its original position resulted in a return of TEE findings to the baseline state in all patients. This series suggests that off-pump CABG can be performed safely in the majority of patients with PFOs; however, additional investigation is needed to assure that adverse effects do not occur in a subset of patients undergoing off-pump CABG in the presence of a PFO. IMPLICATIONS: This case series suggests that coronary artery bypass graft surgery can be safely performed in most patients with patent foramen ovale without the use of a cardiopulmonary bypass.

Adult↗

The effect of chronic cocaine administration on hemodynamic stability and neurohumoral mediators during isoflurane anesthesia and shock in rats.

BACKGROUND: The aim of this investigation was to determine whether chronic cocaine administration altered endogenous vasoconstrictor secretion in response to hypotension from isoflurane anesthesia and blood loss in rats. METHODS: Rats received continuous intravenous infusions of saline (n=11), or cocaine 6 mg kg(-1) d(-1) (n=13) or 18 mg kg(-1) d(-1) (n=12) for 13 days. On day 14, rats were anesthetized with intraperitoneal ketamine and xylazine and a femoral artery catheter and a tracheotomy performed to allow lung ventilation (PaCO2, 30-40 mmHg). After baseline parameters were noted, isoflurane was introduced to end-tidal concentrations of 0.7% for 10 min (1/2 MAC), 1.4% for 10 min (MAC) and again 0.7% for 10 min (1/2 MAC-2) when 5 ml of blood was withdrawn (SHOCK). Blood samples were drawn to assess arterial blood gas indices at various time points as well as plasma epinephrine, angiotensin II and vasopressin at MAC, 1/2 MAC-2 and SHOCK. RESULTS: Rats administered cocaine had higher oxygen extraction, required higher minute ventilation and had lower PaO2 values than rats administered saline despite similar body temperatures and hematocrits. Isoflurane administration resulted in significant dose dependent but similar blood pressure decreases in all study groups. Plasma epinephrine, angiotensin II and vasopressin concentrations were not different in saline or cocaine treated animals at any time point. CONCLUSION: These data suggest that chronic cocaine treatment in rats does not impair endogenous vasoconstrictor secretion nor alter the heart rate and blood pressure response to isoflurane and blood loss.

Anesthesia↗

Desflurane pharmacokinetics during cardiopulmonary bypass.

OBJECTIVE: To describe the washin and washout of desflurane when first administered during cardiopulmonary bypass (CPB) for cardiac surgery. DESIGN: A single-arm prospective study. SETTING: University-affiliated hospital operating room. PARTICIPANTS: Ten adult patients presenting for cardiac surgery. INTERVENTIONS: Consenting patients presenting for cardiac surgery received anesthesia with midazolam and fentanyl. Patients were cooled to 32 degrees C on CPB, then desflurane 6% was administered and blood samples drawn repeatedly from the arterial and venous bypass cannulae as well as from the membrane oxygenator inlet and exhaust from 2 to 32 minutes of desflurane administration. Just before rewarming, final (maximum) washin samples were taken. On rewarming, desflurane was discontinued, and blood and gas samples were taken 2 to 24 minutes thereafter. MEASUREMENTS AND MAIN RESULTS: CPB time was 116 +/- 10 minutes, and ischemic time was 81 +/- 6 minutes. Mean pump flow was 4.49 +/- 0.03 L/min, and mean arterial pressure was 70.1 +/- 1 mmHg during the study period. Arterial washin of desflurane was initially rapid; arterial concentrations reached 50% of administered concentrations within 4 minutes, but then slowed, reaching 68% of inspired concentrations at 32 minutes (desflurane concentration 4.0% +/- 0.3%). Arterial washout of desflurane was more rapid; arterial concentrations fell to 18% of the maximum concentration reached within 4 minutes, and only 8% of the maximum arterial concentration was present in blood 20 minutes later. CONCLUSION: Desflurane showed rapid initial washin and washout on CPB when administration was started at 32 degrees C and stopped at time of rewarming.

Aged↗

Arterial and venous Thrombelastograph variables differ during cardiac surgery.

UNLABELLED: The Thrombelastograph (TEG; Haemoscope Corp., Skokie, IL) coagulation analyzer is an effective point-of-care monitor for routine clinical practice and clinical research. Prior investigators have used either arterial or venous samples of blood for TEG measurements. We conducted this prospective cohort study to determine potential differences in TEG variables between arterial and venous blood samples. Arterial and venous samples were drawn from 40 cardiac surgical patients, yielding 134 pairs for comparison. Twenty-nine comparisons (control) were between arterial and arterial samples and were not significantly different. For the arterial and venous comparisons (n = 105), mean (+/-sd) arterial and venous values were the following: reaction time, 10 +/- 2 mm vs 13 +/- 4 mm, P = 0.004; maximum amplitude, 59 +/- 9 mm vs 49 +/- 12 mm, P < 0.001; alpha angle, 61 +/- 10 degrees vs 51 +/- 14 degrees, P < 0.001; K, 5 +/- 2 mm vs 8 +/- 4 mm, P = 0.007; and lysis, 2.5 +/- 1.7 vs 2.5 +/- 2.0 (not significant), arterial versus venous, respectively. Arterial blood samples demonstrated TEG values reflecting stronger (larger maximum amplitude) and faster (shorter reaction time and K value, wider alpha angle) clot formation. The results suggest that users of TEG coagulation analyzers should be consistent with the site of blood sampling given the potential differences obtained. IMPLICATIONS: Thrombelastograph (TEG) values obtained from venous blood samples differ from values obtained from arterial blood samples. When the TEG coagulation analyzer is used for clinical purposes, it is important to be consistent in the blood collection site.

Adult↗

The pharmacokinetics of anesthetic drugs and adjuvants during cardiopulmonary bypass.

The institution of cardiopulmonary bypass during cardiac surgery has profound effects on the plasma concentration of drugs and thus their therapeutic effectiveness. These changes occur through acute hemodilution, altered plasma protein binding, hypotension, as well as the use of hypothermia and heparin administration. Isolation of the lungs from the circulation and the possible sequestration of drugs in the bypass circuit also affect drug plasma concentrations on bypass. The individual characteristics of the drug in question are also important in determining the final plasma concentration: Lipid soluble drugs with a high volume of distribution may be more readily taken up by bypass equipment, but the initial fall in concentration at the start of cardiopulmonary bypass may be more readily counteracted by back diffusion into plasma, if large tissue stores have accumulated. The extent of the drug's plasma protein binding is of importance as the effective free fraction in plasma for highly bound drugs will be sensitive to changes in plasma protein binding brought on by factors such as hemodilution, heparin administration as well as alpha, acid-glycoprotein binding. Clearly the fate of drugs administered before or on bypass is complex and can only be accurately determined by specific studies evaluating drug plasma concentrations. This review updates the available data on anesthetics and drugs used during cardiac surgery in order that anesthetists may predict better the likely effect of drugs administered before or during cardiopulmonary bypass.

Analgesics, Opioid↗

A rapid, sensitive assay for cocaine and its metabolites in biological fluids using solid-phase extraction and high-performance liquid chromatography.

An improved method for the simultaneous determination of cocaine and its metabolites, benzoylecgonine (BE), norcocaine, and ecgoninemethylester (EME), in rat plasma and urine is described. Following derivatization of EME to p-fluorococaine, chromatography was performed on two high-performance liquid chromatography (HPLC) columns in series (5-microm spheric C8 and 5-microm cyanopropyl) using a mobile phase containing acetonitrile/HPLC water/trifluoroacetic acid (28:72:0.1) with bupivacaine as an internal standard. Quantitation limits were 25 ng/mL for cocaine, BE, and norcocaine and 50 ng/mL for EME using 300-500 microL rat plasma and 500 microL of rat urine. The assay was linear from the limit of quantitation to 2000 ng/mL for cocaine and its metabolites in both plasma and urine samples. Because this method uses a small amount of sample (300 microL plasma or 500 microL of urine), it is applicable to study of the pharmacokinetics and disposition of cocaine and its major metabolites.

Animals↗

Current status of lung volume reduction.

Lung volume reduction surgery, where 20-30% of lung is resected in patients with end-stage emphysema, has been shown in a number of published series to improve expiratory lung volumes, exercise capacity, and subjective well being. This procedure, originally described in the early 1950s, has caught the imagination of the public and medical fraternity. This operation may find utility as an alternative to lung transplantation. Only when the results of a number of randomized clinical trials are available, however, will an assessment of the true value of this procedure be known.

Journal Article↗

Chronic continuous cocaine infusion in rats: effect on urine cocaine, ecgonine methylester and benzoylecgonine concentrations and bolus-dose cocaine pharmacokinetics.

The aim of this study was to determine the effect of chronic cocaine infusion on urine cocaine, ecgonine methylester and benzoylecgonine concentrations to establish if they varied with dose and duration of cocaine administration. Male rats were continuously infused with cocaine at either 6 or 18 mg kg(-1) daily for 13 days. Three urine samples taken over the course of the infusion period showed that cocaine, ecgonine methylester and benzoylecgonine concentrations varied with the dose administered and the duration of administration. Cocaine, ecgonine methylester and benzoylecgonine concentrations were 2-3 times greater in the high-dose group than the low-dose group at each sampling time point. These decreased, respectively, from 7.0+/-1.1, 26.7+/-4.5 and 29.5+/-5.4 microg mL(-1) to 2.5+/-0.5, 10.5+/-1.8 and 11.8+/-1.5 microg mL(-1) in the high-dose group and from 1.0+/-0-2, 7.8+/-1.5 and 6.3+/-0.1 microg mL(-1) to 0.5+/-0.1, 4.0+/-0.6 and 3.1+/-0.4 microg mL(-1) in the low-dose group (P < 0.05) over the infusion period. We also studied the pharmacokinetic and metabolic profile of an intravenous bolus dose of 2.5 mg kg(-1) cocaine hydrochloride after a similar cocaine infusion in rats. Cocaine pharmacokinetics and the profile of ecgonine methylester, benzoylecgonine and norcocaine were no different from rats chronically infused with saline for the same period. Altered cocaine metabolism could not explain the effect of the duration of cocaine infusion on altered metabolite concentrations in urine. Ecgonine methylester/benzoylecgonine urine concentration ratios did not alter with duration of infusion (1.2+/-0.2 and 1.1+/-0.2 in the high-dose group at the first and last time point) and were not affected by the dose of cocaine (1.3+/-0.6 and 1.2+/-0.1 at corresponding times in the low-dose group (P > 0.05)). We conclude that chronic cocaine infusion does not alter cocaine metabolism. This was not reflected by absolute cocaine metabolite urine concentrations, which varied with time, but was represented by urine ecgonine methyl ester/benzoylecgonine concentration ratios.

Anesthetics, Local↗

Anesthesia for left ventricular assist device placement.

Appropriate anesthesia for LVAD placement needs to incorporate an understanding of the surgical procedure and LVAD physiology, the altered physiology and pharmacology of the cardiac failure patient, and a knowledge of the interaction of anesthesia with the potent cardiac drugs used in end-stage heart failure therapy. The anesthesiologist is faced with a critically ill decompensated patient, often with altered renal and hepatic function, but must ensure adequate anesthesia to avoid intraoperative awareness. Intelligent use of TEE can assist the surgeon to pinpoint potential pitfalls of LVAD placement and can have a significant effect on improving outcome in these challenging patients.

Anesthesia↗

A validated stable isotope dilution liquid chromatography tandem mass spectrometry assay for the trace analysis of cocaine and its major metabolites in plasma.

A validated method has been developed for the simultaneous quantitation of cocaine and its major metabolites (ecgonine methyl ester, benzoylecgonine, and norcocaine) in rat plasma. The method is based upon the use of stable isotope dilution liquid chromatography/atmospheric pressure chemical ionization/tandem mass spectrometry. Previously reported methods do not have the sensitivity and specificity that can be attained with this method. Plasma samples required no cleanup apart from protein precipitation, and no derivatization was required. Selected reaction monitoring was performed on the transitions of m/z 200 to m/z 182 (ecgonine methyl ester), m/z 290 to m/z 168 (benzoylecgonine), m/z 304 to m/z 182 (cocaine), and m/z 290 to m/z 168 (norcocaine). The standard curves were linear over the range from 2 ng/mL (benzoylecgonine, cocaine, and norcocaine) or 5 ng/mL (ecgonine methyl ester) to 1000 ng/mL in rat plasma. The lower limit of quantitation (LLQ) for benzoylecgonine, cocaine, and norcocaine was 2 ng/mL, and for ecgonine methyl ester, the LLQ was 5 ng/mL for plasma. This simple, rapid, reliable, and sensitive method of quantitation had excellent accuracy and precision for the four analytes. The method was sensitive enough to permit a detailed study of the pharmacokinetics of cocaine and its metabolites after administration of a bolus intravenous dose to rats.

Animals↗

Cocaine, norcocaine, ecgonine methylester and benzoylecgonine pharmacokinetics in the rat.

We have compared the pharmacokinetics of bolus dose cocaine administration with that of its three most important metabolites; norcocaine, ecgonine methylester, and benzoylecgonine and assessed whether kinetics are dose dependent at two equimolar doses equivalent to cocaine hydrochloride 2.5 and 5 mg/kg respectively. Forty-nine male Sprague-Dawley rats were randomly divided into 8 groups to receive i.v. either high (14.7 umol/kg) (HI) or low (7.3 umol/kg) (LO) bolus doses of cocaine or one of its metabolites. Arterial blood samples for cocaine and metabolite analysis were taken repetitively over the next 3 h. Equimolar bolus doses of these congeners showed biexponential plasma concentration decay curves which were fitted to a two compartment model and subjected to noncompartmental analysis. The plasma concentration time profiles were significantly different for the HI and LO doses administered for each congener. The elimination half-lives of cocaine and norcocaine were similar (28-33 min), that for ecgonine methylester (60-71 min) was approximately twice this and for benzoylecgonine was 40-44 min. Cocaine clearance (155-158 ml/kg/min) was found to be in the range found in other rat studies. Ecgonine methylester clearance and benzoylecgonine clearance were found to be one quarter and one eighth of this value respectively. The pharmacokinetic profile of these congeners was not dose dependent when the two doses administered were compared.

Animals↗

Influence of infused catecholamines on the pharmacokinetics of cocaine and benzoylecgonine formation after bolus dose or continuous cocaine administration in the rat.

The purpose of this study was to determine whether a catecholamine infusion administered to simulate a stress state could alter the pharmacokinetics of administered cocaine and effect the formation of benzoylecgonine, its major metabolite, in the rat. In a previous investigation we determined that catecholamine infusion enhanced the toxicity of continuous cocaine infusion by reducing the time before the onset of convulsions and respiratory arrest. We postulated that this enhanced toxicity was an effect of catecholamines on the pharmacokinetics of cocaine. To test this hypothesis we studied plasma cocaine and benzoylecgonine disposition after intravenous bolus administration of cocaine (5 mg kg(-1)) to 19 male Sprague-Dawley rats and to 10 rats which received an initial loading-dose cocaine infusion of 1 mg kg(-1) min(-1) (for 5 min) followed by continuous infusion of 100 microg kg(-1) min(-1). Rats in both studies randomly received either continuous catecholamine infusion comprising adrenaline (7.25 microg mL(-1)), noradrenaline (4.4 microg mL(-1)) and dopamine (8.0 microg mL(-1)) or saline, administered at a similar rate. Bolus dose cocaine administration, simultaneously with catecholamine infusion, resulted in significantly higher Cmax levels for cocaine (3.8 compared with 2.5 microg mL(-1)) and lower distribution half-lives (3.3 compared with 5.9 min) and central compartment volumes of distribution (1.5 compared with 2.1 L kg(-1)) compared with saline infusion. Benzoylecgonine formation was significantly reduced in rats receiving catecholamines whereas the elimination half-lives (26.3 compared with 25.0 min) and systemic clearances (146 compared with 146 mL kg(-1) min(-1)) were not different. Continuous cocaine infusion (after an initial loading infusion) resulted in the doubling of plasma cocaine levels in rats receiving catecholamines compared with the control group. These data indicate that elevated plasma catecholamines have significant effects on cocaine pharmacokinetics. This might serve to explain the enhanced toxicity from concomitant cocaine and catecholamine infusion demonstrated in previous experiments.

Animals↗