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Introduction: Operating suites are multidisciplinary units par excellence, and mostly they are the most expensive units in hospitals. Interdisciplinary workflow and efficiency are therefore crucial, which is influenced by floor plans varying from hospital to hospital. Most operating rooms are equipped with adjacent induction rooms, allowing preparation and anesthesia induction of the next patient, while the previous patient is still in the operating room. Parallelizing the working steps is thought to improve turn-over time, thus increasing throughput, number of cases and finally revenue. However, this assumption has never been challenged. Methods: We analyzed workflow during regular working hours in an operating suite equipped with a mixture of operating rooms (OR) with next door induction rooms and operating rooms without induction rooms. This allows a direct comparison of both structural elements for efficiency using utilization data over a 24-months period. Both settings were used for gynecological operations. Results: Key result is that induction rooms do not improve perioperative workflow including turn-over time. Instead, ORs without adjacent induction rooms have a significantly shorter turn-over time and OR occupancy duration per case, although surgical time and staffing were similar. Discussion: Adjacent induction rooms require extra space, funding, and high maintenance costs, but they do not speed up peri-operative processes. Modern anesthetic techniques allow for fast induction of and emergence from anesthesia. Induction rooms adjacent to the OR are no longer needed if general anesthesia without extended monitoring is used for the majority of cases.
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STUDY OBJECTIVE: We explored the feasibility of a Clinical Decision Support System (CDSS) to guide evidence-based perioperative anticoagulation. DESIGN: Prospective randomised clinical management simulation multicentre study. SETTING: Five University and 11 general hospitals in Germany. PARTICIPANTS: We enrolled physicians (anaesthesiologist (n = 73), trauma surgeons (n = 2), unknown (n = 1)) with different professional experience. INTERVENTIONS: A CDSS based on a multiple-choice test was developed and validated at the University Hospital of Frankfurt (phase-I). The CDSS comprised European guidelines for the management of anticoagulation in cardiology, cardio-thoracic, non-cardio-thoracic surgery and anaesthesiology. Phase-II compared the efficiency of physicians in identifying evidence-based approach of managing perioperative anticoagulation. In total 168 physicians were randomised to CDSS (PERI-KOAG) or CONTROL. MEASUREMENTS: Overall mean score and association of processing time and professional experience were analysed. The multiple-choice test consists of 11 cases and two correct answers per question were required to gain 100% success rate (=22 points). MAIN RESULTS: In total 76 physicians completed the questionnaire (n = 42 PERI-KOAG; n = 34 CONTROL; attrition rate 54%). Overall mean score (max. 100% = 22 points) was significantly higher in PERI-KOAG compared to CONTROL (82 ± 15% vs. 70 ± 10%; 18 ± 3 vs. 15 ± 2 points; P = 0.0003). A longer processing time is associated with significantly increased overall mean scores in PERI-KOAG (≥33 min. 89 ± 10% (20 ± 2 points) vs. <33 min. 73 ± 15% (16 ± 3 points), P = 0.0005) but not in CONTROL (≥33 min. 74 ± 13% (16 ± 3 points) vs. <33 min. 69 ± 9% (15 ± 2 points), P = 0.11). Within PERI-KOAG, there is a tendency towards higher results within the more experienced group (>5 years), but no significant difference to less (≤5 years) experienced colleagues (87 ± 10% (19 ± 2 points) vs. 78 ± 17% (17 ± 4 points), P = 0.08). However, an association between professional experience and success rate in CONTROL has not been shown (71 ± 8% vs. 70 ± 13%, 16 ± 2 vs. 15 ± 3 points; P = 0.66). CONCLUSIONS: CDSS significantly improved the identification of evidence-based treatment approaches. A precise usage of CDSS is mandatory to maximise efficiency.
Subject(s)
Decision Support Systems, Clinical , Physicians , Anticoagulants/adverse effects , Hospitals, University , Humans , Prospective StudiesABSTRACT
The anesthesiologist, who traditionally was solely responsible for the intra- and postoperative care of patients, has undergone a transformation over the last decades and has emerged as a specialist for perioperative medicine. This includes preoperative assessment, preoperative stabilization of emergent cases, pre- or postoperative initiation of regional blocks, postoperative recovery and if needed postoperative intensive care outside the intensive care unit. A traditional recovery room, designated to take care of patients emerging from anesthesia only, no longer matches the modern anesthesiologist's demands. However, a traditional recovery room can easily be transformed into a vibrant multi-purpose perioperative care unit. Especially in smaller hospitals, this serves to match the anesthesiologist's demands without the financial burden of separate units for each task. On the contrary, it allows to transform the recovery room from a mandatory, but costly postoperative unit into a highly productive and demanding perioperative unit, allowing for extra revenues without corresponding costs. Worldwide, operating rooms are linked to an adjacent recovery room allowing patients to emerge from anesthesia until they fulfill the criteria to be transferred either to the regular ward or, in case of outpatient surgery, to be discharged home. Running these recovery rooms, however, is expensive due to the required technical equipment and the monthly costs of highly qualified anesthesia personnel. Despite these financial burdens, such recovery rooms are still mandatory to ensure full recovery after anesthesia and surgery. In most countries, there is no (full) reimbursement for providing recovery rooms, turning them into fiscally deficient units in most hospitals. However, recovery rooms can be further developed allowing hospitals to improve their caseloads, reduce turnover times in the operating room, and even help to manage a shortage of beds in the intensive care unit. In this paper, we describe the potential transformation from a traditional recovery room to a multi-purpose perioperative high-tech unit.
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During the COVID-19 pandemic, the number of patients who require intensive care treatment may outnumber the number of intensive care beds, even in industrialized nations. Consequently, triage may become necessary. In Italy, France, and Spain, age has been used as a leading parameter to decide who is admitted to the intensive care unit, and who receives palliative care. Although age is an objective and easy-to-use parameter, it is ethically not ideal to withdraw ventilator therapy from elderly people who suffer from COVID-19. We have developed a simple and easy-to-use scoring system to allow for triage that is based upon scientific outcome data and, at the same time, fulfills ethical standards.
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Bed Occupancy , COVID-19 , Health Care Rationing/ethics , Intensive Care Units , Pandemics , Triage/ethics , Aged , France , Hospital Bed Capacity , Humans , Italy , SARS-CoV-2 , Spain , Triage/methodsABSTRACT
Anaesthetists are in increasing frequency confronted with patients equipped with cardiac implantable electrical devices. A consensus conference standardized the handling of such patients for elective cases. However, this multidisciplinary approach is characterized by a complexity, which is hard to handle in emergency cases and even in nowadays clinical routine. However, risks associated with electrocautery or electromagnetic interference can be easily handled applying a significantly easier approach. Telemetric reprogramming and/or postoperative interrogation of the cardiac implanted eletronical device can be avoided in most cases.
Subject(s)
Defibrillators, Implantable , Pacemaker, Artificial , Patient Safety/standards , Perioperative Care/standards , Practice Guidelines as Topic , Contraindications , Evidence-Based Medicine , Germany , HumansSubject(s)
Acute Lung Injury/drug therapy , Arginine Vasopressin/administration & dosage , Pneumonia/prevention & control , Vasoconstrictor Agents/administration & dosage , Acute Lung Injury/mortality , Animals , Disease Models, Animal , Dose-Response Relationship, Drug , Humans , Nitric Oxide/metabolism , Pneumonia/drug therapy , Risk Factors , Sheep , Sheep, Domestic , Survival Rate , Treatment OutcomeABSTRACT
OBJECTIVE: Atrial natriuretic peptide is regarded as an important regulator of pulmonary vasomotor tone and permeability. This study investigated the role of atrial natriuretic peptide in sepsis-associated pulmonary pathophysiology. DESIGN: Prospective experimental investigation. SETTING: Laboratory at a university hospital. SUBJECTS: Twelve awake, chronically instrumented sheep. INTERVENTIONS: The sheep were instrumented with lung lymph fistulas and received a continuous infusion with live Pseudomonas aeruginosa for 48 hrs. After 40 hrs, the atrial natriuretic peptide-receptor antagonist HS-142-1 was continuously infused in the HS-124-1 group (3 mg/kg/hr, n = 6) for 8 hrs, whereas the control group received the carrier (n = 6). MEASUREMENTS AND MAIN RESULTS: Lung lymph flow was markedly elevated in response to sepsis after 40 hrs in both groups. Atrial natriuretic peptide-receptor blockade further increased lymph flows by 41 +/- 17% (41 hrs) up to 64 +/- 20% (44 hrs, p < .05) in the presence of normal permeability to protein. Although mean pulmonary artery pressure increased (p < .05 vs. 40 hrs), capillary pressure remained unaffected. Despite identical fluid balances in both groups, cardiovascular filling variables significantly increased in the HS-142-1 group. This was associated with increasing cardiac index and mean arterial pressure (p < .05 vs. 40 hrs). In the control group, all variables remained constant between 41 and 48 hrs. CONCLUSION: Blockade of atrial natriuretic peptide receptors increases pulmonary transvascular fluid flux independent of changes in permeability to protein in chronic ovine sepsis. Atrial natriuretic peptide may therefore play a protective role for the alveolar-capillary barrier during sepsis.
Subject(s)
Atrial Natriuretic Factor/metabolism , Lung/physiology , Pseudomonas Infections/drug therapy , Pulmonary Edema/drug therapy , Pulmonary Edema/physiopathology , Receptors, Atrial Natriuretic Factor/antagonists & inhibitors , Animals , Atrial Natriuretic Factor/analysis , Disease Models, Animal , Female , Lymphatic System/drug effects , Lymphatic System/physiology , Male , Permeability/drug effects , Pulmonary Circulation/drug effects , Pulmonary Circulation/physiology , Reference Values , Risk Factors , Sensitivity and Specificity , Sepsis/drug therapy , Sepsis/microbiology , Sheep, DomesticABSTRACT
BACKGROUND: It is still unclear as to whether the paradoxical arteriovenous carboxyhemoglobin (COHb) difference found in critical illness may represent a novel marker of the acute inflammatory response. We determined whether the arterial and central venous COHb concentration or their difference may be correlated to classical pro-inflammatory markers. METHODS: Arterial and matched central venous blood gases were obtained from non-smoking intensive care patients undergoing gastrointestinal surgery, and were correlated with plasma concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP) and leukocytes. RESULTS: No correlation was found between arteriovenous COHb difference and the investigated pro-inflammatory mediators. While arterial and central venous COHb concentrations were positively correlated to plasma concentrations of TNF-alpha (P< or =0.01), IL-6 (P<0.05) and PCT (P< or =0.01), they were neither interrelated with PCT nor with leukocytes. CONCLUSIONS: Arteriovenous COHb difference does not appear to be a marker of the acute inflammatory response. Future studies are needed to investigate whether arterial and central venous COHb concentrations by themselves may serve as indicators of systemic inflammation.
Subject(s)
C-Reactive Protein/metabolism , Calcitonin/metabolism , Carboxyhemoglobin/metabolism , Critical Illness , Interleukin-6/metabolism , Leukocytes/metabolism , Protein Precursors/metabolism , Tumor Necrosis Factor-alpha/metabolism , Blood Gas Analysis , Calcitonin Gene-Related Peptide , Female , Humans , Inflammation Mediators , Male , Middle AgedABSTRACT
BACKGROUND: Nowadays, the collection of PBPCs by apheresis from healthy donors is a routine method. The mobilization with rHu G-CSF and the apheresis procedures are usually well tolerated without severe side effects. STUDY DESIGN AND METHODS: We report a severe complication in a 41-year-old unrelated female donor who was allowed to donate PBPCs and was mobilized with 10 microg of G-CSF per kg per day. During PBPC apheresis, she experienced a circulatory arrest after 132 minutes and processing of 7078 mL of blood (twice the donor's blood volume). RESULTS: Immediate cardiopulmonary resuscitation restored sinus rhythm and regulatory respiration without sequelae. Subsequent cardiologic examinations (heart catheterization, electrophysiologic testing, tilting table test) resulted in the diagnosis of a neurocardiogenic syncope. Other cardiac or circulatory disorders could be excluded. The implantation of a cardiac pacemaker was recommended to the donor. The 4-year-old recipient was successfully transplanted with the partial product collected until the arrest occurred. The patient received a total of 2.54 x 106 CD34+ cells per kg of body weight. CONCLUSION: After exclusion of other cardiac diseases, the diagnosed neurocardiogenic syncope probably induced the circulatory arrest during apheresis rather than the administration of G-CSF.
Subject(s)
Blood Component Removal/adverse effects , Heart Arrest/etiology , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells/cytology , Adult , Female , Graft vs Host Disease/prevention & control , Granulocyte Colony-Stimulating Factor/adverse effects , HumansABSTRACT
Norepinephrine (NE) is mostly used to treat severe hypotension. However, NE has potentially adverse vasoconstrictive effects on regional vascular beds of kidney, liver, and gut, with a potential for ensuing organ dysfunction. NE therefore is considered as a last reserve in otherwise refractory hypotension. During sepsis, a loss of catecholamine responsiveness occurs that is often interpreted as down-regulation of catecholamine receptors. Therefore, the doses of NE needed to maintain or restore blood pressure may be extremely high. Surprisingly, no adverse vasoconstriction with subsequent hypoperfusion occurs during sepsis, despite the high doses of NE administered. Instead, NE rather causes an increase in blood flow and oxygen delivery.
Subject(s)
Norepinephrine/therapeutic use , Sepsis/drug therapy , Vasoconstrictor Agents/therapeutic use , Blood Pressure/drug effects , Humans , Norepinephrine/adverse effects , Norepinephrine/physiology , Sepsis/physiopathology , Vasoconstriction/drug effects , Vasoconstrictor Agents/adverse effectsABSTRACT
UNLABELLED: The origin of cerebral dysfunction in patients with sepsis is still unclear. However, altered cerebral perfusion may play an important role in its pathogenesis. Using an established, chronic model of hyperdynamic ovine sepsis, we examined cerebral perfusion in 20 sheep subjected to a continuous infusion of live Pseudomonas aeruginosa. After 24 h of sepsis, the hypotensive sheep (reduction in mean arterial blood pressure by 16%; P < 0.05) received the nitric oxide synthase inhibitor N(G)-mono-methyl-L-arginine (L-NMMA; 7 mg. kg(-1). h(-1); n = 7), norepinephrine (NE; n = 7), or normal saline (control; n = 6). NE infusion was individually targeted to achieve the same increase in mean arterial blood pressure as that observed in matched sheep of the L-NMMA group. Regional perfusion was measured by using colored microspheres. Although L-NMMA caused a significant increase in systemic vascular resistance index (1167 +/- 104 versus 793 +/- 59 dyne. cm(-5). m(2); P < 0.05), it caused a change neither in cerebrovascular resistance nor in cerebral blood flow. When related to systemic blood flow, a redistribution of blood flow to the brain became obvious. The NE-associated increase in systemic blood pressure (98 +/- 5 versus 83 +/- 5; P < 0.05) was accompanied by an increase in cardiac output (7.8 +/- 0.5 versus 6.7 +/- 0.6; P < 0.05) and, hence, systemic perfusion. However, blood flow to the brain remained unaffected. Although detrimental vasoconstrictive effects of NE and L-NMMA, including cerebral hypoperfusion, are discussed, neither drug had any effect on cerebral perfusion during experimental hyperdynamic sepsis. IMPLICATIONS: Cerebral dysfunction is often found in septic patients. In this regard, it is debated whether vasopressor drugs, such as norepinephrine and L(G)-mono-methyl-L-arginine, have harmful effects on the cerebral circulation. During experimental hyperdynamic sepsis, however, neither drug altered cerebral vascular resistance or cerebral blood flow.
Subject(s)
Cerebrovascular Circulation/physiology , Enzyme Inhibitors/therapeutic use , Nitric Oxide Synthase/antagonists & inhibitors , Norepinephrine/therapeutic use , Pseudomonas Infections/drug therapy , Pseudomonas Infections/physiopathology , Vasoconstrictor Agents/therapeutic use , omega-N-Methylarginine/therapeutic use , Animals , Blood Pressure/drug effects , Female , Heart Rate/drug effects , Microspheres , Nitric Oxide Synthase Type I , Regional Blood Flow/drug effects , Renal Circulation/drug effects , Sheep , Vascular Resistance/drug effectsABSTRACT
OBJECTIVE: Critically ill patients who develop multiple organ failure during systemic inflammatory states are often predisposed to hypovolemia and vasoconstrictor therapy. Although numerous investigations have evaluated the sequelae of systemic inflammation, no data are available on the contribution of chronic vasoconstrictor-masked hypovolemia to organ dysfunction and morphology. DESIGN: Prospective, randomized laboratory investigation. SETTING: University research laboratory. SUBJECTS: Eighteen adult chronically instrumented sheep. INTERVENTIONS: The animals were randomly assigned to one of three groups. In the norfenefrine-masked hypovolemia plus endotoxemia (NMH+ENDO) group, mean arterial pressures of 80 mm Hg were maintained by using the alpha1-adrenergic catecholamine norfenefrine for 52 hrs during hypovolemia. Hypovolemia was induced by hemorrhage (about 23 mL x kg(-1)) until mean arterial pressures reached 40 mm Hg. Endotoxin (0.5 microg x k(-1)) was then injected after 4, 16, 28, and 40 hrs. The NMH group received norfenefrine-masked hypovolemia but no endotoxin. In the ENDO group, recurrent endotoxemia was induced during normovolemia. MEASUREMENTS AND MAIN RESULTS: Despite profound differences in fluid management, cardiovascular filling pressures were not statistically different between groups. Endotoxemia induced norfenefrine-refractory shock (p < .05 vs. the other groups) and contributed to renal dysfunction only during vasoconstrictor-masked hypovolemia. Norfenefrine-masked hypovolemia caused disseminated cardiac cell necrosis independent of endotoxemia (p < .05 vs. ENDO). CONCLUSIONS: Hypovolemia can be masked when volume status is monitored by filling pressures. In this new model of endotoxemia-associated multiple organ failure, chronic vasoconstrictor-masked hypovolemia turned systemic inflammation into a life-threatening condition with renal and cardiovascular failure. Cardiomyocyte necroses were caused by vasoconstrictor-masked hypovolemia but were unrelated to cardiovascular failure.
Subject(s)
Adrenergic alpha-Agonists/adverse effects , Disease Models, Animal , Endotoxemia/complications , Endotoxemia/drug therapy , Hypovolemia/etiology , Multiple Organ Failure/etiology , Octopamine/analogs & derivatives , Octopamine/adverse effects , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/drug therapy , Vasoconstrictor Agents/adverse effects , Animals , Blood Pressure/drug effects , Blood Volume/drug effects , Critical Illness , Endotoxins/adverse effects , Female , Hypovolemia/diagnosis , Hypovolemia/mortality , Incidence , Multiple Organ Failure/diagnosis , Multiple Organ Failure/mortality , Prospective Studies , Random Allocation , Recurrence , Risk Factors , Salmonella typhi , Sheep , Survival Analysis , Vascular Resistance/drug effectsABSTRACT
UNLABELLED: Chronic ingestion of small doses of ethanol protects the myocardium from ischemic damage. It was demonstrated that short-term administration of ethanol (SAE) enhances the recovery of stunned myocardium in acutely instrumented, anesthetized dogs. It is unclear whether this beneficial effect of SAE also occurs in awake dogs. Therefore, we investigated the effects of SAE on regional myocardial stunning in awake dogs. Thirty-six dogs were chronically instrumented for measurement of heart rate, left atrial, aortic, and left ventricular pressure, left systolic ventricular contactility (dP/dt(max)) and diastolic ventricular function (dP/dt(min)), and regional myocardial wall-thickening fraction (WTF). Occluders around the left anterior descending (LAD) artery allowed the induction of reversible ischemia in the LAD-perfused myocardium. The dogs were assigned to one of three groups that differed in the dose of ethanol administered in the ethanol experiment (I, 0.125 g/kg [n = 12]; II, 0.25 g/kg [n = 12]; III, 0.5 g/kg [n = 12]). In each group, the dogs underwent two ischemic episodes (randomized crossover fashion; separate days): 10 min of LAD occlusion after the application of ethanol IV over 30 min (ethanol group) and without ethanol (control). WTF and hemodynamic variables were measured at baseline and at predetermined time points until complete recovery of myocardial stunning occurred. LAD-ischemia led to a significant decrease of LAD-WTF in all groups. There was no difference in WTF and hemodynamic variables with or without SAE during reperfusion. We conclude that SAE (0.125 g/kg, 0.25 g/kg, and 0.5 g/kg) does not significantly affect myocardial stunning in conscious dogs. IMPLICATIONS: In contrast to previous experiments in anesthetized dogs, short-term administration of ethanol does not alter myocardial stunning in conscious dogs.
Subject(s)
Central Nervous System Depressants/pharmacology , Ethanol/pharmacology , Myocardial Stunning/physiopathology , Animals , Central Nervous System Depressants/blood , Coronary Circulation/drug effects , Coronary Circulation/physiology , Dogs , Electrophysiology , Ethanol/blood , Female , Male , Manometry , Myocardial Reperfusion Injury/physiopathology , Myocardial Stunning/pathology , Myocardium/pathology , Ventricular Function, Left/physiologyABSTRACT
IMPLICATIONS: Animal-experimental studies demonstrate desflurane's trigger effect for malignant hyperthermia (MH). In contrast to other anesthetics, the time interval from exposure to the occurrence of symptoms is much longer with desflurane. This case report focuses on MH induced by desflurane alone.
Subject(s)
Anesthesia, Inhalation/adverse effects , Anesthetics, Inhalation/adverse effects , Isoflurane/analogs & derivatives , Isoflurane/adverse effects , Malignant Hyperthermia/physiopathology , Adolescent , Biopsy , Dantrolene/therapeutic use , Desflurane , Female , Hemodynamics/drug effects , Humans , In Vitro Techniques , Malignant Hyperthermia/blood , Malignant Hyperthermia/drug therapy , Monitoring, Intraoperative , Muscle Relaxants, Central/therapeutic use , Muscle, Skeletal/drug effects , Orthopedic Procedures , Postoperative Period , Scoliosis/surgeryABSTRACT
PURPOSE OF REVIEW: For years, the field of sepsis research was extremely active; the net result, however, was rather disappointing. Sepsis is still a major problem in intensive care units worldwide. Frustratingly, sepsis is characterized by a high morbidity and mortality. Although multiple (animal) studies with promising results have been published, the clinical situation has changed only a little. However, the recent 2 or 3 years of sepsis research brought significant results that will have a significant impact on clinical routine. RECENT FINDINGS: In the last 2 years, three big randomized controlled clinical trials were published on treatment of sepsis, each leading to a significant improvement in outcome: administration of activated protein C, administration of low dose corticosteroids, and maintenance of strict normoglycemia. SUMMARY: A breakthrough in sepsis research was long awaited. Recent clinical studies demonstrated that an improvement in outcome can be achieved even with simple means. This review focuses on these new therapeutic concepts, hopefully helping to transfer scientific advantages into everyday clinical routine.
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It is still unclear whether the paradoxical arteriovenous carboxyhemoglobin (COHb) difference found in critical illness is due to increased COHb production by the lung, or whether this gradient is caused by technical artifacts using spectrophotometry. In healthy and matched endotoxemic sheep, blood gases were analyzed with a standard ABL 625 and the updated version, an ABL 725. The latter one was accurately calibrated for COHb wavelengths (SAT 100) to eliminate the FCOHb dependency on oxygen tension. All endotoxemic sheep exhibited a hypotensive-hyperdynamic circulation and a pulmonary hypertension. Interestingly, arteriovenous COHb difference occurred in both healthy and endotoxemic sheep (P<0.001 each). Arterial and central venous COHb concentrations determined with the ABL 625 were significantly lower than those measured with the ABL 725 (P<0.001 each). We conclude that (a) arteriovenous COHb difference per se does not reflect critical illness and (b) measurements with an ABL 625 underestimate COHb concentrations.
Subject(s)
Carboxyhemoglobin/metabolism , Critical Illness , Animals , Biomarkers , Blood Gas Analysis/instrumentation , Blood Gas Analysis/methods , Endotoxemia/blood , Female , Hypertension, Pulmonary/blood , Oxygen/metabolism , Prospective Studies , SheepSubject(s)
Catheterization, Central Venous/methods , Adult , Child , Electrocardiography , Guidelines as Topic , HumansABSTRACT
Adrenomedullin (AM) is a vasodilatory peptide hormone, playing a key role in the regulation of cardiovascular homeostasis. In view of the circulatory failure in sepsis, it is still debated as to whether the occurrence of vascular hyporeactivity against AM plays a causative or protective role. This study was designed as a prospective, controlled trial to elucidate the hemodynamic response following a titrating infusion of human AM in healthy and endotoxemic sheep. ANOVA demonstrated that AM infusion produced hypotension and tachycardia, and increased cardiac index in a dose-dependent manner, both in healthy and endotoxemic sheep. In addition, AM application reduced pulmonary vascular resistance index in ovine endotoxemia (P=0.02). These findings confirm that AM produces a hyperdynamic circulation, in the presence and absence of systemic inflammation. Further, exogenous AM could possibly be a useful adjunct in the common setting of sepsis-associated pulmonary hypertension.
Subject(s)
Endotoxemia/physiopathology , Hemodynamics/drug effects , Peptides/pharmacology , Adrenomedullin , Animals , Infusions, Intravenous , Peptides/administration & dosage , Prospective Studies , SheepABSTRACT
Following systemic inflammation, the lung induces an isoenzyme of heme oxygenase (HO-1), catalyzing carbon monoxide (CO) production through breakdown of heme molecules. However, it is still debated why the paradoxical arterio-venous carboxyhemoglobin (COHb) difference occurs only during critical illness but not in healthy volunteers. To elucidate whether oxygen fractions at (sub-)physiologic ranges alter the affinity of CO to hemoglobin (Hb), we performed an in vitro laboratory experiment, in which we exposed venous blood samples to fixed CO-doses at incrementing oxygen fractions (FiO2). ANOVA demonstrated that the affinity of CO (200 and 400 ppm) to Hb progressively increased with an FiO2 from 0% to 15%, whereas at higher oxygen tensions this effect vanished. This might explain why the arterio-venous COHb difference found in critically ill patients is not reproducible in healthy adults, since the latter ones are characterized by higher venous oxygen saturations.