Circulatory Stability Research Articles

Right Ventricle to Pulmonary Artery Conduit Reduces Interim Mortality After Stage 1 Norwood for Hypoplastic Left Heart Syndrome

Despite significant improvement in survival after stage 1 Norwood, interim mortality before the second-stage operation remains significant. On the basis of reports of improved circulatory stability associated with the use of a right ventricle to pulmonary artery conduit, the difference between two physiologically different sources of pulmonary blood flow on interim mortality was investigated. Data collection of 96 consecutive hospital survivors after stage 1 Norwood surgery was undertaken. The source of pulmonary blood flow was a modified right Blalock-Taussig shunt in 46 (BTS) and a right ventricle to pulmonary artery conduit in 50 patients. The same follow-up protocol was used in both groups. Data analysis was performed to identify variables associated with interim mortality. Analysis of patient-related and procedure-related variables revealed no differences in age, weight, diagnosis, presence of aortic atresia, lowest perioperative pH, duration of cardiopulmonary bypass, circulatory arrest, length of mechanical ventilation, or hospital stay at the time of stage 1 Norwood between groups. Respiratory rate and systolic blood pressure were the only differences detected between groups at the time of discharge. Interim mortality was higher in the Blalock-Taussig shunt group. Statistical analysis identified aortic atresia, a modified Blalock-Taussig shunt, and the presence of perioperative dysrhythmias to be associated with interim mortality. The use of a right ventricle to pulmonary artery shunt decreases the incidence of interim mortality among hospital survivors after stage 1 Norwood for hypoplastic left heart syndrome. Aortic atresia, the use of a modified Blalock-Taussig shunt, and perioperative dysrhythmias are independently associated with a higher mortality before superior cavopulmonary connection.

Biology of adenovirus and its use as a vector for gene therapy.

ADENOVIRUSES WERE FIRST DISCOVERED half a century ago by Rowe and colleagues, who were trying to culture adenoid tissue in the laboratory (Rowe et al., 1953). Since that time, nonhuman adenoviruses have been isolated from a number of species including chimpanzees, pig, mouse, and dog, as well as other mammalian and avian species (Shenk, 1996). Although human adenoviruses cause significant levels of respiratory, ocular, and gastrointestinal disease, they have been the object of intense study over the years mainly as a model system for basic eukaryotic cellular processes such as transcription, RNA processing, DNA replication, translation, and oncogenesis. Early on, it was shown that the virus could recombine during growth in culture (Lewis et al., 1966a,b; Pierce et al., 1968; Lewis and Rowe, 1970), ultimately setting the stage for the use of the virus as a vector for gene delivery into cells, animals, and humans. Many features of adenovirus make it well suited for gene delivery, including the ability to grow recombinant viruses to high titers, a relatively high capacity for transgene insertion, and efficient transduction of both quiescent and actively dividing cells, usually without incorporation of viral DNA into the host cell genome. These characteristics, as well as the development of many methods for manipulating the viral genome, have made adenovirus a popular choice as a gene delivery vehicle. This is evidenced by the fact that adenovirus is currently being used in roughly one-quarter of all gene therapy clinical trials, making it second only to the use of retroviral vectors (Journal of Genetic Medicine Website, www. wiley.co.uk/genmed/clinical). In this review, we summarize our current understanding of the life cycle of the human adenoviruses and then discuss how the structure and function of viral genes impact the use of the virus as a gene delivery vehicle. Readers desiring a more comprehensive coverage of the biology of the virus are directed to the volumes edited by Doerfler and Bohm (2003, 2004). VIRUS STRUCTURE

Low prime Cardiopulmonary Bypass (CPB): Contributing factors impairing effectiveness

Objectives: Low prime setups (LPS) drain venous blood directly into the arterial pump omitting venous reservoirs. Potential benefits of theses systems are improved circulatory stability, reduced inflammation, decreased vasoconstrictive agents and less hemodilution. Objective of this study was to analyse two different LPS retrospectively.

Effects of General Anesthetics on Regulation of the Peripheral Vasculature

The heart is a passively filling pump in a circulatory system that is connected in series with distensible blood vessels. Therefore, systemic blood pressure and tissue perfusion depend upon adequate peripheral vascular tone as well as myocardial function. Likewise, pharmacologic agents that alter circulatory stability can affect one or both of these components. The generalized depressor effects of general anesthetics have been well known clinically for over 50 years. Moreover, there are many similarities in basic cellular regulatory mechanisms among the different tissue types, and general anesthetics are well known to distribute freely among the perfusion-rich tissues (eg, central nervous system, cardiovascular system, and renal system). Therefore, it is likely that the hemodynamic depression resulting from the systemic administration of anesthetics results from actions on regulatory mechanisms of the peripheral vasculature as well as on the heart. The peripheral vasculature is regulated by extrinsic neural, endothelial, and humoral mechanisms, which interact with each other as well as with intrinsic membrane and intracellular systems within the vascular smooth muscle cell. Different general anesthetics have been found to act on specific mechanisms at each of these levels. However, the large number and complexity of these known mechanisms, as well as the many anesthetic agents, has made it extremely difficult to determine which are significant in terms of the meaningful mechanisms that are responsible for anesthetic action, major side effects, or both. Current knowledge about the effects of general anesthetics on both the extrinsic intrinsic regulatory mechanisms of peripheral vascular control is reviewed.

Targeting hepatocytes for drug and gene delivery: emerging novel approaches and applications.

The asialoglycoprotein receptor (ASGP-R) on mammalian hepatocytes provides a unique means for the development of liver-specific carriers, such as liposomes, recombinant lipoproteins, and polymers for drug or gene delivery to the liver, especially to hepatocytes. The abundant receptors on the cells specifically recognize ligands with terminal galactose or N-acetylgalactosamine residues, and endocytose the ligands for an intracellular degradation process. The use of its natural ligand, i.e. asialofetuin, or synthetic ligands with galactosylated or lactosylated residues, such as galactosylated cholesterol, glycolipids, or galactosylated polymers has achieved significant targeting efficacy to the liver. There are several examples of successful targeted therapy for acute liver injury with asialofetuin-labeled and vitamin E-associated liposomes or with a caspase inhibitor loaded in sugar-carrying polymer particles, as well as for the delivery of a new antiviral agent, 9-(2-phosphonylmethoxyethyl)adenine. Liposome-mediated gene delivery to the liver is more difficult than to other organs, such as to lungs. It is still in its infancy due to difficulties in solving general issues, such as the circulatory stability of liposome-DNA complexes, and lysosomal or endosomal degradation of plasmid DNA. In spite of these existing concerns, several new approaches offer some reason for optimism, for example; intravenous injection of asialofetuin- or galactosylated cholesterol-labeled cationic liposomes has led to high transgene expression in the liver. In addition, specific antisense oligonucleotides against woodchuck hepatitis viruses incorporated into sialoorosomucoid-poly-L-lysine significantly inhibited viral replication in the liver. Finally, galactosylated polymers are promising for gene delivery, but require further studies to verify their potential applications.

Secretion of biologically active glycoforms of bovine follicle stimulating hormone in plants.

We chose the follicle stimulating hormone (FSH), a pituitary heterodimeric glycoprotein hormone, as a model to assess the ability of the plant cell to express a recombinant protein that requires extensive N-glycosylation for subunit folding and assembly, intracellular trafficking, signal transduction and circulatory stability. A tobacco mosaic virus (TMV) based transient expression system was used to express a single-chain (sc) version of bovine FSH in the tobacco related species Nicotiana benthamiana. Preparations of periplasmic proteins from plants infected with recombinant viral RNA contained high levels of sc-bFSH, up to 3% of total soluble proteins. Consistently, in situ indirect immunofluorescence revealed that the plant cell secreted the mammalian secretory protein to the extracellular compartment (EC). By mass spectrometric analysis of immunoaffinity purified sc-bFSH derived from EC fractions, we found two species of the plant paucimannosidic glycan type, truncated forms of complex-type N-glycans. Stimulation of cAMP production in a CHO cell line expressing the porcine FSH receptor acknowledged the native-like structure of sc-bFSH and a sufficient extent of N-glycosylation required for signal transduction. Furthermore, in superovulatory treatments of mice, sc-bFSH displayed significant in vivo bioactivity, although much lower than that of pregnant mare serum gonadotropin. We conclude that plants may have a broad utility as hosts for the recombinant expression of proteins even where glycosylation is essential for function.

Application of “double bridge mechanical” resuscitation for profound cardiogenic shock leading to cardiac transplantation

Background. In patients with acute profound cardiogenic circulatory failure unresponsive to conventional resuscitation, we instituted immediate aggressive application of extracorporeal membrane oxygenation (ECMO) to restore circulatory stability. Long-term hemodynamic support was accomplished with an early “bridge” to ventricular assist device (VAD) before definitive treatment with cardiac transplantation. Methods. A respective review of ECMO and VAD data registries was instituted. Results. From May 1996 to July 2000, 23 patients were placed on ECMO support for profound cardiogenic circulatory failure. Eleven patients (47%) were withdrawn from support due to severe neurologic injury or multisystem organ failure. Three patients (13%) were weaned off ECMO with good outcome. Nine patients (39%) were transferred to a VAD. Two patients expired while on VAD support, and 7 of the VAD-supported patients (78%) survived to transplantation. Overall survival was 43%. Conclusions. Emergent ECMO support is a salvage approach for cardiac resuscitation once conventional measures have failed. In neurologically intact patients, the early transfer to a VAD quickly stabilizes hemodynamics, avoids complications, and is essential for long-term circulatory support before definitive treatment with cardiac transplantation.

Interactions between cardiovascular treatments and anaesthesia

Circulatory stability is one of the main objectives of the perioperative management of high-risk patients. Most of these patients are chronically treated with cardiovascular treatments, which interfere with the functioning of several physiological systems aimed at maintaining the circulatory status when the loading conditions of the heart deteriorate, or limit the compensatory mechanisms used when metabolic needs increase. Taking into account the pharmacology of these medications, their repercussions on perioperative haemodynamics and their potential beneficial effects on regional circulations, it has become possible to determine whether or not they must be given or withdrawn perioperatively.

A retrospective examination of regional plus general anesthesia in children undergoing open heart surgery.

The use of regional anesthesia in combination with general anesthesia for children undergoing cardiac surgery is receiving increasing attention from clinicians. The addition of regional anesthesia may improve clinical outcomes and decrease costs as a result of the reduced need for postoperative mechanical ventilation. The goal of this retrospective chart review was to evaluate whether spinal anesthesia (SAB) or epidural anesthesia (EPID) in combination with general anesthesia was associated with circulatory stability, satisfactory postoperative sedation/analgesia, and a low incidence of adverse effects. The medical records of 50 consecutive children having open heart surgery with SAB or EPID and general anesthesia between September 1996 and December 1997 were reviewed. We found no significant differences in the incidence of clinically significant changes in vital signs, oxygen desaturation, hypercarbia, or vomiting. Patients in the SAB group received significantly more sedative/analgesic interventions than those in the EPID group.

Prospective of human butyrylcholinesterase as a detoxifying antidote and potential regulator of controlled-release drugs

Butyrylcholinesterase from human plasma (HuBChE) is a potential drug candidate that can be employed in several therapeutic fields. This is attributed to the unique structure of the enzyme that allows selective accommodation of a variety of substrates and inhibitors, some of which are excluded from the catalytic gorge of acetylcholinesterase. Enhancement of endogenous levels of HuBChE can protect against the toxicity of organophosphate pesticides and nerve agents, reduce risks of complications due to cocaine abuse, reverse muscle relaxant-induced apnea following surgery anesthesia, and alleviate symptoms caused by local anesthetics. It can be used either prophylactically or as a treatment drug. Treatment with HuBChE offers replacement therapy of traditional pharmacological antidotes that suffer from several disadvantages. In addition, endogenous HuBChE is capable of biotransformation of ester- or carbamate-bond containing prodrugs to active therapeutic molecules, and has the potential of improvement of bioavailability and safety of numerous drugs with sales records. In certain cases HuBChE may be administered before, with, or after the prodrug. HuBChE is absorbed in high yield from muscles and its circulatory stability is sufficient to provide significant therapeutic levels for several days, even after a single dose load. Based on limited studies with partially purified HuBChE, the enzyme seems to lack significant physiological incompatibilities in humans that may prevent its use as a drug. Clinical trials aimed at providing pharmacokinetic data and evaluation of safety issues of acute and chronic administration of purified HuBChE are expected to advance the concept of using the enzyme as a multipurpose drug. Drug Dev. Res. 50:298–308, 2000. © 2000 Wiley-Liss, Inc.

Catechol activation in the vasomotor center upon emergence from anesthesia: specificity.

The rostral ventrolateral medulla (RVLM) controls the vascular system. It may contribute to postoperative hypertension observed upon emergence from anesthesia. This structure contains adrenergic cardiovascular neurons. Therefore, one question was addressed: does a change in RVLM catechol activity occur upon emergence from anesthesia? Halothane-anesthetized, paralyzed rats had their ventilatory, circulatory, and acid-base stability controlled. All pressure points and incisions were infiltrated with local anesthetic. With in vivo electrochemistry, a catechol signal was recorded in the RVLM in the following circumstances: (1) under stable halothane anesthesia for 120 minutes (halothane group), (2) during 120 minutes after halothane discontinuation (saline-emergence group), (3) during 60 minutes after halothane discontinuation followed by 60 minutes after halothane readministration (readministration group), (4) emergence in rats treated with atenolol and nitroprusside to hold blood pressure as close as possible to baseline, (5) emergence after morphine 1 mg.kg(-1) i.v., (6) emergence after decerebration, and (7) emergence upon recording in the mid-brain dopaminergic A10 area. Stable halothane anesthesia (n = 6) led to no change in mean arterial pressure (MAP), heart rate (HR), and catechol signal (CAOC). During emergence from anesthesia (n = 6), MAP, HR, and catechol signal increased and did not return to baseline. By contrast, a return of MAP, HR, and catechol signal to baseline was observed upon readministration of halothane (n = 6). Whereas blood pressure and heart rate were maintained as closely as possible to baseline, a large catechol activation (n = 5) was observed upon emergence from anesthesia. A catechol activation from a lowered baseline was observed upon emergence following morphine administration (n = 5). A minor circulatory activation without RVLM catechol activation was observed upon emergence following decerebration (n = 5). Recordings in the A10 area revealed no increase in the catechol signal following emergence (n = 5). Adrenergic RVLM neurons appear to be responsive upon emergence from anesthesia, possibly being activated by suprapontine afferents impinging on the RVLM.

The Effects of Intraoperative Intravenous Clonidine on Fluid Requirements, Hemodynamic Variables, and Support During Liver Transplantation

In this prospective, nonblind study, we report the use of clonidine during orthotopic liver transplantation (OLT).Twenty adult patients in a stable medical condition were studied. General anesthesia consisted of isoflurane in air/oxygen and sufentanil. Patients in the clonidine group received a slow IV infusion (15 min) of 4 [micro sign]g/kg clonidine during induction. The other patients were used as controls. IV fluid requirements were determined as follows: albumin (4% solution) was administered to maintain filling pressures to a pulmonary capillary wedge pressure (PCWP) of more than 12 mm Hg. Packed red blood cells were transfused to maintain a hemoglobin level of 8-9 g/dL. Circulatory stability was evaluated using: systolic and diastolic arterial blood pressure and heart rate recorded at 2-min intervals; and the vasopressor/inotropic support required to maintain adequate hemodynamic variables after reperfusion. Intraoperative albumin and packed red blood cell requirements were significantly reduced in patients in the clonidine group (1644 +/- 140 and 50 +/- 50 mL vs 2867 +/- 226 mL and 1350 +/- 443 mL; P < 0.05). Heart rate was significantly slower in patients of the clonidine group. There were no differences in systolic arterial blood pressure. After reperfusion, patients in the control group showed significantly lower diastolic arterial blood pressure, required more vasopressor/inotropic support, and were more acidotic than patients in the clonidine group. We conclude that the administration of 4 [micro sign]g/kg clonidine during induction of OLT significantly reduced the intraoperative requirements of IV fluids and blood products without compromising circulatory stability. Improvement in immediate reperfusion-induced disturbances was observed. Implications: The administration of 4 [micro sign]g/kg clonidine during induction of liver transplantation significantly reduced the intraoperative requirements for IV fluids and blood products without compromising the circulatory stability. Improvement in immediate reperfusion-induced disturbances was also observed. (Anesth Analg 1998;86:468-76)

Catecholamine activation in the vasomotor center on emergence from anesthesia: the effects of alpha2 agonists.

The rostral ventrolateral medulla (RVLM) controls the vascular system and may contribute to postoperative hypertension. It comprises adrenergic cardiovascular neurons, a site for action of alpha2-adrenergic agonists. Because alpha2 agonists minimize perioperative circulatory activation, we asked the following question: do alpha2 agonists, such as clonidine and mivazerol, blunt the catecholamine activation observed in the RVLM on emergence from anesthesia? Halothane-anesthetized, paralyzed rats had their ventilatory, circulatory, and acid-base stability controlled. All pressure points and incisions were infiltrated with local anesthetics. With in vivo electrochemistry, a catechol signal was recorded in the RVLM during 150 min of stable halothane anesthesia (saline-halothane group); for 120 min after halothane discontinuation (saline-emergence group); after emergence and administration of the reference alpha2 agonist, clonidine 7 microg/kg or 21 microg/kg I.V. (50% or 90% effective dose [ED50 or ED90], respectively); and after emergence and administration of a new alpha2 agonist, mivazerol 20 microg/kg or 150 microg/kg I.V. (ED50 or ED90). Under halothane, dose-response curves for the RVLM catecholamine signal were constructed for mivazerol and an alpha2 antagonist, idazoxan (ED50 2.3 mg/kg I.V.). Stable halothane anesthesia (n = 5) led to no change in mean arterial pressure (MAP), heart rate (HR), or catechol signal (CAOC). During emergence from anesthesia, the MAP, HR, and CAOC increased (n = 5). Clonidine led to a near total suppression of the RVLM catecholamine activation noticed on emergence from anesthesia (n = 5). Hypertension was partially blunted with clonidine 7 microg/kg (n = 5). Tachycardia was partially blunted with mivazerol 20 microg/kg (n = 5). Pretreatment with idazoxan suppressed all the effects of mivazerol (n = 5). On emergence from anesthesia, alpha2 agonists modify the activity of adrenergic cardiovascular neurons located within the vasomotor center, as assessed by in vivo electrochemistry. We provide a rationale for the use of alpha2 agonists on emergence from anesthesia in coronary/hypertensive patients.

Role of oligosaccharides in the pharmacokinetics of tissue-derived and genetically engineered cholinesterases.

To understand the role of glycosylation in the circulation of cholinesterases, we compared the mean residence time of five tissue-derived and two recombinant cholinesterases (injected intravenously in mice) with their oligosaccharide profiles. Monosaccharide composition analysis revealed differences in the total carbohydrate, galactose, and sialic acid contents. The molar ratio of sialic acid to galactose residues on tetrameric human serum butyrylcholinesterase, recombinant human butyrylcholinesterase, and recombinant mouse acetylcholinesterase was found to be approximately 1.0. For Torpedo californica acetylcholinesterase, monomeric and tetrameric fetal bovine serum acetylcholinesterase, and equine serum butyrylcholinesterase, this ratio was approximately 0.5. However, the circulatory stability of cholinesterases could not be correlated with the sialic acid-to-galactose ratio. Fractionation of the total pool of oligosaccharides obtained after neuraminidase digestion revealed one major oligosaccharide for human serum butyrylcholinesterase and three or four major oligosaccharides in other cholinesterases. The glycans of tetrameric forms of plasma cholinesterases (human serum butyrylcholinesterase, fetal bovine serum acetylcholinesterase, and equine serum butyrylcholinesterase) clearly demonstrated a reduced heterogeneity and higher maturity compared with glycans of monomeric fetal bovine serum acetylcholinesterase, dimeric tissue-derived T. californica acetylcholinesterase, and recombinant cholinesterases. T. californica acetylcholinesterase, recombinant cholinesterases, and monomeric fetal bovine serum acetylcholinesterase showed a distinctive shorter mean residence time (44-304 min) compared with tetrameric forms of plasma cholinesterases (1902-3206 min). Differences in the pharmacokinetic parameters of cholinesterases seem to be due to the combined effect of the molecular weight and charge- and size-based heterogeneity in glycans.

Ropivacaine 7.5 mg/ml for elective Caesarean section. A clinical and pharmacokinetic comparison of 150 mg and 187.5 mg

The new, long-acting local anaesthetic ropivacaine has shown less systemic toxicity than bupivacaine and a concentration of 7.5 mg/ml can therefore be used for epidural anaesthesia in Caesarean section. The present pilot study was undertaken to find indications for an optimal dosage by comparing the clinical effects, quality of anaesthesia and pharmacokinetics of ropivacaine 150 mg (lower dose = LD) vs 187.5 mg (higher dose = HD) for women undergoing elective Caesarean section under epidural anaesthesia. Sixteen full-term women scheduled for elective Caesarean section in two equal-sized consecutive groups received 20 or 25 ml ropivacaine epidurally in this non-randomised, open study. Study parameters included sensory and motor blockade, circulatory response, intraoperative pain and discomfort, neonatal evaluation and pharmacokinetic determinations. Block height varied between T5 and T2 in the LD group, whereas the HD group produced 4 unnecessarily high blocks (C8 in 3 women and C7 in 1 woman). Surgical anaesthesia was excellent in both groups. Circulatory stability was pronounced in the LD group (no ephedrine given), while 4 women required ephedrine in the HD group. Neonatal outcome as judged by Apgar scores; umbilical blood gas determinations and NACS scores were excellent in both groups. The plasma concentration-time profiles indicated linearity in the concentration range studied, with similar clearance values to those reported previously. Placental drug equilibrium was rapid; however, the foetal drug exposure depended on intrauterine exposure time. 20-25 ml ropivacaine 7.5 mg/ml produced very satisfactory conditions for elective Caesarean section under epidural anaesthesia. In this small population, 150 mg ropivacaine seemed optimal, while 187.5 mg produced unnecessarily extended block height in 50% of the women.

Clonidine for Major Vascular Surgery in Hypertensive Patients

The utility of clonidine for hypertensive patients presenting for major vascular procedures remains debatable.Twenty-one hypertensive patients presenting for aortic surgery were given clonidine (n = 11) or placebo (n = 10) in a double-blind, randomized manner. Clonidine was administered 6 micro gram/kg per os 120 min before induction of anesthesia and 3 micro gram/kg intravenously (IV) over 60 min from aortic declamping to skin closure. Anesthesia was induced with alfentanil 20 micro gram/kg, midazolam, and atracurium and maintained with nitrous oxide 70%, an alfentanil infusion (0.25 micro gram centered dot kg-1 centered dot min-1), and isoflurane. Anesthetic requirements, circulatory variables, interventions, and isoproterenol dose-response curves (pre- and postoperatively) were determined. Plasma concentrations of clonidine, alfentanil, and vasoactive hormones were measured. When the clonidine group was compared with the placebo group, (a) isoflurane, alfentanil, and midazolam requirements were reduced by 38%, 42%, and 41%, respectively (P = 0.04, 0.03, 0.0002, respectively); (b) supplemental circulatory and anesthetic adjustments were reduced by 51% (P = 0.0006); (c) interventions with vasopressors were not significantly increased (placebo: two; clonidine: five); (d) systolic and mean arterial pressures and heart rate were reduced; (e) increases in norepinephrine, epinephrine, and plasma renin activity were suppressed, whereas vasopressin surge was attenuated; and (f) chronotropic response to isoproterenol was unaffected. Clonidine was effective in reducing anesthetic requirements and in improving circulatory stability in hypertensive patients presenting for major vascular procedures. (Anesth Analg 1996;83:687-95)

Effect of anesthesia and surgery on plasma cytokine levels

Cytokines released in response to stress may have a profound impact on circulatory stability. There is no information on the effect of general anesthesia alone on plasma cytokine levels and little information on cytokine release following surgery. Plasma cytokine levels and hemodynamic parameters were measured during anesthesia and abdominal surgery under sterile and nonpyrogenic conditions in seven pigs anesthetized with ketamine and pentobarbital. Tumor necrosis factor (TNF) was measured by bioassay. Bioassays of low and high sensitivity were used to measure interleukin 6 (IL-6). Measurements were made sequentially during: (1) 4 hours observation with anesthesia alone; (2) 2 hours following laparotomy and traumatic intestinal manipulation (IM) sufficient to produce shock; and (3) after an intravenous bolus of 1 μg/kg endotoxin as a positive control. Arterial blood pressure decreased following IM from 91.5 ±- 5.8 to 48.6 ±- 3.2 mm Hg, (mean ±- SE, P < .05), with no further change following endotoxin. Heart rate was unchanged during the experiment, and central venous pressure decreased after endotoxin ( P < .05). There were no increases in TNF or IL-6 (using a low sensitivity assay) with anesthesia alone or following IM with shock, but both increased after endotoxin administration ( P < .05); using a high sensitivity assay, IL-6 did not change during anesthesia alone but did increase fivefold following IM with shock ( P < .05) and 50-fold following endotoxin administration ( P < .05). We conclude that in a porcine model under sterile and nonpyrogenic conditions, prolonged anesthesia does not increase plasma cytokine levels. Traumatic manipulation of the intestines sufficient to cause diffuse bowel injury and shock causes only small increases in plasma IL-6. Substantial increases in both TNF and IL-6 occur following a minimal endotoxin challenge showed an intact functional systemic response.

Unreliability of blood pressure and heart rate to evaluate cardiac output in emergency resuscitation and critical illness

To evaluate the reliability of the vital signs to evaluate circulatory stability as reflected by cardiac index. Descriptive analysis based on data gathered prospectively, using a predetermined protocol. University-run county hospital, with a large trauma service. Sixty-one high-risk trauma patients with accidental injury who were studied immediately after admission to the Emergency Department, and subsequently, 163 critically ill postoperative ICU patients. Standard fluid therapy, usually crystalloids, but occasionally packed red cell transfusions and colloids, as indicated by clinical criteria. Arterial BP was measured by pressure transducer and arterial catheter; heart rate (HR) was measured by electrocardiograph signal, and cardiac output was measured by thermodilution. In sudden severe hypovolemic hypotension, the mean arterial pressure (MAP) nadir (lowest) roughly correlated (r2 = .25) with flow, but there was poor correlation (r2 = .0001) when all pressure and flow values were evaluated. The pressure and flow values were obtained throughout the course of the hypotensive episodes during the initial resuscitation in ICU patients and during terminal illnesses. Observations at the time of acute severe hypotensive crises that show rough correlation of MAP and cardiac index should not be extrapolated throughout the entire hypotensive period or to other less extreme clinical situations. The stress response to hypovolemia, with endogenous catecholamines and neural mechanisms, tends to maintain arterial pressure in the face of decreasing flow for a variable period of time. However, when these mechanisms are overwhelmed by prolonged hypovolemia, the pressure decreases precipitously, but not synchronously, with flow. We conclude that blood flow cannot reliably be inferred from arterial pressure and heart rate measurements until extreme hypotension occurs.

Anesthetic management with eptazocine hydrobromide in patients receiving long-term antipsychotic medication.

We evaluated the usefulness of eptazocine hydrobromide as an adjuvant in patients receiving antipsychotics for long periods. Patients anesthetized with enflurane alone (enflurane group, n = 11), were compared with those anesthetized with enflurane and eptazocine hydrobromide 1 mg.kg(-1) (eptazocine group, n = 10). The mean daily dose of the antipsychotics, converted into the amount of chlorpromazine, was 345 mg in the eptazocine group and 366 mg in the enflurane group. The duration of antipsychotic medication was 14 years in the eptazocine group and 17 years in the enflurane group. The maintenance concentration of enflurane was 0.37% in the eptazocine group and 0.67% in the enflurane group, being significantly lower in the former group. The interval between the termination of operation and removal of the endotracheal tube was slightly shorter in the eptazocine group. The discriminant function of circulatory stability obtained from the measurement of systolic blood pressure and heart rate during anesthesia in the eptazocine group was 481, being significantly lower than 539 in the enflurane group. Both absolute and relative instabilities of systolic blood pressure and heart rate were slightly smaller in the eptazocine group. No side effects associated with eptazocine hydrobromide administration were observed. These results suggest the safety and usefulness of this analgesic in the anesthetic management of patients receiving long-term antipsychotic medication.

Circulatory stability and plasma lidocaine levels during continuous and intermittent thoracic epidural analgesia.

Circulatory stability and plasma levels of lidocaine were investigated in 20 patients who received thoracic epidural analgesia with plain lidocaine during elective abdominal surgery under general anesthesia. In one group, bolus injection of 8 ml of 2% lidocaine was followed by volumetric continuous pump-driven infusion (CPI) of 8 ml of 1.5% lidocaine per hour. In the other group, the same initial bolus injection was followed by repetitive intermittent bolus infusions (RII) of 6 ml of 1.5% lidocaine at a 45 min-interval. Circulatory stability was evaluated by a discriminant function. The results showed that epidural analgesia produced smaller circulatory fluctuations with CPI than with RII. Venous plasma lidocaine levels were consistently higher with CPI than with RII. Plasma levels increased stepwise with RII and kept constant with CPI. Differences in plasma levels were significant from 20 min after the initial injection to 135 min. We therefore conclude that epidural analgesia with CPI is superior to that with RII. However, it must be remembered that higher plasma levels may occur with CPI than with RII.