Strategies for interpreting arterial blood gases.

ABSTRACT: This article provides a step-by-step guide for nurses to interpret arterial blood gas (ABG) results, focusing on five key components: SaO2, PaO2, pH, PaCO2, and HCO3-. It explains how to assess a patient's oxygenation status, compensation levels, and determine if there is an acid-base disturbance and if that disturbance is respiratory or metabolic.

Single-cell O2 exchange imaging shows that cytoplasmic diffusion is a dominant barrier to efficient gas transport in red blood cells.

Disorders of oxygen transport are commonly attributed to inadequate carrying capacity (anemia) but may also relate to inefficient gas exchange by red blood cells (RBCs), a process that is poorly characterized yet assumed to be rapid. Without direct measurements of gas exchange at the single-cell level, the barriers to O2 transport and their relationship with hematological disorders remain ill defined. We developed a method to track the flow of O2 in individual RBCs by combining ultrarapid solution switching (to manipulate gas tension) with single-cell O2 saturation fluorescence microscopy. O2 unloading from RBCs was considerably slower than previously estimated in acellular hemoglobin solutions, indicating the presence of diffusional barriers in intact cells. Rate-limiting diffusion across cytoplasm was demonstrated by osmotically induced changes to hemoglobin concentration (i.e., diffusive tortuosity) and cell size (i.e., diffusion pathlength) and by comparing wild-type cells with hemoglobin H (HbH) thalassemia (shorter pathlength and reduced tortuosity) and hereditary spherocytosis (HS; expanded pathlength). Analysis of the distribution of O2 unloading rates in HS RBCs identified a subpopulation of spherocytes with greatly impaired gas exchange. Tortuosity imposed by hemoglobin was verified by demonstrating restricted diffusivity of CO2, an acidic gas, from the dissipative spread of photolytically uncaged H+ ions across cytoplasm. Our findings indicate that cytoplasmic diffusion, determined by pathlength and tortuosity, is a major barrier to efficient gas handling by RBCs. Consequently, changes in RBC shape and hemoglobin concentration, which are common manifestations of hematological disorders, can have hitherto unrecognized and clinically significant implications on gas exchange.

A prospective, randomized trial of intravenous hydroxocobalamin versus noradrenaline or saline for treatment of lipopolysaccharide-induced hypotension in a swine model.

Early, non-clinical studies support the use of hydroxocobalamin to treat sepsis-induced hypotension, but there is no translational, large animal model. The objective of this study was to compare survival in a sepsis model where large swine had endotoxaemia induced with lipopolysaccharide (LPS) and were treated with intravenous hydroxocobalamin (HOC), noradrenaline (NA), or saline. Thirty swine (45-55 kg) were anaesthetized, intubated, and instrumented with continuous femoral and pulmonary artery pressure monitoring. Hypotension, predefined as 50% of baseline, was induced with LPS. Animals then received HOC, NA, or saline and monitored for 3 hours. The main outcome was survival to the conclusion of the study. Using a power of 80% and an alpha of 0.05, 10 animals were used per group. Secondary outcomes included: mean arterial pressure (MAP), systemic vascular resistance (SVR) and cardiac output (CO) along with several markers of sepsis. No differences were detected between groups at baseline or after hypotension. The survival distributions of the three groups were significantly different with more HOC animals surviving (10/10) compared with NA (8/10) or Saline (5/10) (log-rank P < 0.03). MAP was found to be higher in both the HOC and NA groups and HOC achieved the highest SVR. In this large animal, translational study of an endotoxaemic model of sepsis, hydroxocobalamin improved survival when compared with saline.

The Gradient Perfusion Model Part 1: Why and at what sites decompression sickness can occur.

INTRODUCTION: Decompression sickness (DCS) is manifested by the quantity and location of bubbles in body tissues after reduction in ambient pressures. Models have been formulated to explain why bubbles form, but none provide satisfactory explanations as to why the findings of DCS occur as they do. This first of a three-part series explains why and at what sites DCS occurs. MATERIALS AND METHODS: Over a 50-year span and 500 cases of DCS we have managed, it has become apparent that almost all "unexplained" DCS (i.e., cases with no obvious explanation as to how/why they occurred) have physiological explanations. The vagaries of the physiology of tissue perfusion and the physics of gradients as a cause of autochthonous bubble formation were analyzed. FINDINGS: Perfusion is highly variable, with so-called "fast" tissues (i.e., tissues with a rapid rate of saturation) requiring a constant blood supply, "intermediate" tissues requiring a blood supply proportional to needs, and "slow" tissues having minimal perfusion requirements. The 5-liter blood volume in a vascular system with greater than a 20-liter capacity requires careful regulation. Disruptions in the regulation and/or overwhelming gradients explain why DCS occurs. CONCLUSIONS: Our Gradient-Perfusion Model provides an explanation as to why disordering events account for almost all cases of unexplained DCS. We propose that this latter term be discarded and "disordering events" be sought for DCS cases that have no obvious explanations.

In Vitro Evaluation of Pediatric Hollow-Fiber Membrane Oxygenators on Hemodynamic Performance and Gaseous Microemboli Handling: An International Multicenter/Multidisciplinary Approach.

The objective of this study was to compare the hemodynamic performances and gaseous microemboli (GME) handling ability of two pediatric oxygenators in a simulated pediatric cardiopulmonary bypass (CPB) model and the importance of adding an arterial filter in the circuit. The circuit consisted of a Braile Infant oxygenator or a Maquet Quadrox-I Pediatric oxygenator without integrated arterial filter (parallel arrangement), 1/4 in. ID tubing A-V loop, and a 12-Fr arterial cannula, primed with lactated Ringer's solution and packed red blood cells. Trials were conducted at flow rates ranging from 500 to 2000 mL/min (500 mL/min increment) at 35°C and 28°C. Real-time pressure and flow data were recorded using a custom-based data acquisition system. For GME testing, 5 cc of air was manually injected into the venous line. GME were recorded using the Emboli Detection and Classification Quantifier (EDAC) System. An additional experiment using a separate arterial filter was conducted. There was no difference in the mean circuit pressure, pressure drop, total hemodynamic energy level, and energy loss between the two oxygenators. The venous line pressures were higher in the Braile than in the Quadrox group during all trials (P <0.01). GME count and volume at pre-/post oxygenator and pre-cannula sites in the Quadrox were lower than the Braile group at high flow rates (P < 0.05). In the additional experiment, an arterial filter captured a significant number of microemboli at all flow rates. The Braile Infant oxygenator has a matched hemodynamic characteristic with the Quadrox-i Pediatric oxygenator. The Quadrox-i has a better GME handling ability compared with the Braile Infant oxygenator. Regardless of type of oxygenator an additional arterial filter decreases the number of GME.

Anesthesia of Epinephelus marginatus with essential oil of Aloysia polystachya: an approach on blood parameters.

This study investigated the anesthetic potential of the essential oil (EO) of Aloysia polystachya in juveniles of dusky grouper (Epinephelus marginatus). Fish were exposed to different concentrations of EO of A. polystachya to evaluate time of induction and recovery from anesthesia. In the second experiment, fish were divided into four groups: control, ethanol and 50 or 300 µL L-1 EO of A. polystachya, and each group was submitted to induction for 3.5 min and recovery for 5 or 10 min. The blood gases and glucose levels showed alterations as a function of the recovery times, but Na+ and K+ levels did not show any alteration. In conclusion, the EO from leaves of A. polystachya is an effective anesthetic for dusky grouper, because anesthesia was reached within the recommended time at EO concentrations of 300 and 400 µL L-1. However, most evaluated blood parameters showed compensatory responses due to EO exposure.

Diffusive shunting of gases and other molecules in the renal vasculature: physiological and evolutionary significance.

Countercurrent systems have evolved in a variety of biological systems that allow transfer of heat, gases, and solutes. For example, in the renal medulla, the countercurrent arrangement of vascular and tubular elements facilitates the trapping of urea and other solutes in the inner medulla, which in turn enables the formation of concentrated urine. Arteries and veins in the cortex are also arranged in a countercurrent fashion, as are descending and ascending vasa recta in the medulla. For countercurrent diffusion to occur, barriers to diffusion must be small. This appears to be characteristic of larger vessels in the renal cortex. There must also be gradients in the concentration of molecules between afferent and efferent vessels, with the transport of molecules possible in either direction. Such gradients exist for oxygen in both the cortex and medulla, but there is little evidence that large gradients exist for other molecules such as carbon dioxide, nitric oxide, superoxide, hydrogen sulfide, and ammonia. There is some experimental evidence for arterial-to-venous (AV) oxygen shunting. Mathematical models also provide evidence for oxygen shunting in both the cortex and medulla. However, the quantitative significance of AV oxygen shunting remains a matter of controversy. Thus, whereas the countercurrent arrangement of vasa recta in the medulla appears to have evolved as a consequence of the evolution of Henle's loop, the evolutionary significance of the intimate countercurrent arrangement of blood vessels in the renal cortex remains an enigma.

Control of lung ventilation following overwintering conditions in bullfrogs, Lithobates catesbeianus.

Ranid frogs in northern latitudes survive winter at cold temperatures in aquatic habitats often completely covered by ice. Cold-submerged frogs survive aerobically for several months relying exclusively on cutaneous gas exchange while maintaining temperature-specific acid-base balance. Depending on the overwintering hibernaculum, frogs in northern latitudes could spend several months without access to air, the need to breathe or the chemosensory drive to use neuromuscular processes that regulate and enable pulmonary ventilation. Therefore, we performed experiments to determine whether aspects of the respiratory control system of bullfrogs, Lithobates catesbeianus, are maintained or suppressed following minimal use of air breathing in overwintering environments. Based on the necessity for control of lung ventilation in early spring, we hypothesized that critical components of the respiratory control system of bullfrogs would be functional following simulated overwintering. We found that bullfrogs recently removed from simulated overwintering environments exhibited similar resting ventilation when assessed at 24°C compared with warm-acclimated control bullfrogs. Additionally, ventilation met resting metabolic and, presumably, acid-base regulation requirements, indicating preservation of basal respiratory function despite prolonged disuse in the cold. Recently emerged bullfrogs underwent similar increases in ventilation during acute oxygen lack (aerial hypoxia) compared with warm-acclimated frogs; however, CO2-related hyperventilation was significantly blunted following overwintering. Overcoming challenges to gas exchange during overwintering have garnered attention in ectothermic vertebrates, but this study uncovers robust and labile aspects of the respiratory control system at a time point correlating with early spring following minimal to no use of lung breathing in cold-aquatic overwintering habitats.

Eccentric exercise 48 h prior to simulated diving has no effect on vascular bubble formation in rats.

PURPOSE: Decompression sickness (DCS) caused by vascular bubble formation is a major risk when diving. Prior studies have shown that physical exercise has a significant impact in both reducing and increasing bubble formation. There is limited knowledge about the mechanisms, but there are indications that exercise-induced muscle injury prior to diving may cause increased bubble formation. The purpose of this study was to investigate the role of exercise-induced muscle injury as a possible mechanism of bubble formation during diving. METHODS: Muscle injury was induced by exposing female Sprague-Dawley rats (n = 30) to a single bout of eccentric exercise, 100 min intermittent, downhill (-16°) treadmill running. Forty-eight hours later, the animals were exposed to a 50-min simulated saturation dive (709 kPa) in a pressure chamber, when the degree of muscle injury and inflammation would be the most pronounced. Bubble formation after the dive was observed by ultrasonic imaging for 4 h. RESULTS: No difference in bubble loads was found between the groups at any time despite evident muscle injury. Maximum bubble loads (bubbles cm(-2) heart cycle(-1)) were not different, exercise: 1.6 ± 3.5 SD vs control: 2.2 ± 4.1 SD, P = 0.90, n = 15 in each group. CONCLUSIONS: Eccentric exercise performed 48 h prior to diving causes skeletal muscle injury but does not increase the amount of vascular bubbles in rats. The prevailing recommendation is that physical activity prior to diving is a risk factor of DCS. However, present and previous studies implicate that pre-dive physical activity does not increase the DCS risk.

Risk factors for bowel necrosis in patients with hepatic portal venous gas.

PURPOSE: To evaluate the risk factors for bowel necrosis in adult patients with hepatic portal venous gas (HPVG). METHODS: This retrospective study comprised 33 adult patients treated for HPVG between August, 2008 and December, 2011. The patients were divided into a necrotic group (n = 14) and a non-necrotic group (n = 19). We analyzed the clinical demographics, laboratory data, multi-detector computed tomography findings, treatments, and outcomes in each group. RESULTS: Abdominal pain, peritoneal signs, systolic blood pressure, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase (LDH), small intestinal dilatation, poor enhancement of the bowel wall, and intestinal pneumatosis were all significantly associated with bowel necrosis. Moreover, there were significantly more operative cases and deaths in the necrotic group. Multivariate analysis revealed that systolic BP (p = 0.048), LDH (p = 0.022), and intestinal pneumatosis (p = 0.038) were independent risk factors for bowel necrosis. Thus, we created new diagnostic criteria for bowel necrosis based on these three factors, the sensitivity, specificity, and accuracy of which were 100, 78.9, and 87.9 %, respectively. CONCLUSIONS: This study demonstrates new and important findings to evaluate the risk factors for bowel necrosis. Using our diagnostic criteria, the indications for emergency laparotomy can be established more accurately.

Centrifugal pump performance during low-flow extracorporeal CO2 removal; safety considerations.

AIM: The aim of this study was to examine the hydrodynamic performance and gaseous microemboli (GME) activity of two centrifugal pumps for possible use in low-flow extracorporeal CO2 removal. MATERIALS & METHODS: The performance of a Rotassist 2.8 and a Rotaflow 32 centrifugal pump (Maquet Cardiopulmonary AG, Hirrlingen, Germany) was evaluated in a water-glycerine mixture-filled in vitro circuit that enabled measurement of pressures and GME at the pump inlet and pump outlet. Pressure-flow curves were acquired in a 1,000 to 5,000 rpm range while increasing drainage resistance in one series and outlet resistance in another. RESULTS: Respective minimum pump inlet and maximum pump outlet pressures were -539 mmHg and 754 mmHg for the Rotassist 2.8 and -606 mmHg and 806 mmHg for the Rotaflow 32. Maximum standard deviations on pump pressures and flow amounted to 3.0 mmHg and 0.03 L/min, respectively, regardless of pump type and drainage or outlet resistance. The GME at the pump outlet were detectable at pump inlet pressures below -156 mmHg at 0.2 L/min and 2,500 rpm for the Rotassist 2.8 and below -224 mmHg at 0.9 L/min and 3,000 rpm for the Rotaflow 32. CONCLUSION: Both the Rotassist 2.8 and Rotaflow 32 centrifugal pumps show a comparably high hydrodynamic stability, but potential GME formation with decreasing pump inlet pressures should be taken into account to ensure safe centrifugal pump-based low-flow extracorporeal CO2 removal.

Adopting European Network for Health Technology Assessments (EunetHTA) core model for diagnostic technologies for improving the accuracy and appropriateness of blood gas analyzers' assessment.

BACKGROUND: Point-of-care testing (POCT) is a successful methodology for meeting clinical expectations of rapid and accurate results. Scientific literature has moreover highlighted and confirmed the necessity of individuating the best technological solution, in accordance with clinical requirements and contextualized to the whole health organization, where it will be implemented. Health Technology Assessment (HTA) can assist in reaching an appropriate and contextualized decision on a health technology. The aim of this study is to adapt a HTA core model for improving the evaluation of a POCT technology: blood gas analyzers. METHODS: The European Network for Health Technology Assessment (EUnetHTA) core model for diagnostic technologies was applied for evaluating globally marketed blood gas analyzers. Evaluation elements were defined according to available literature and validated using the Delphi method. RESULTS: A HTA model of 71 issues, subdivided into 26 topics and 10 domains, was obtained by interviewing 11 healthcare experts over two rounds of Delphi questionnaires. Ten context parameters were identified in order to define the initial scenario from which the technology assessment was to begin. CONCLUSIONS: The model presented offers a systematic and objective structure for the evaluation of blood gas analyzers, which may play a guidance role for healthcare operators approaching the evaluation of such technologies thus improving, in a contextualized fashion, the appropriateness of purchasing.

Can the oxygenator screen filter reduce gaseous microemboli?

Gaseous microemboli (GME) define small bubbles as < 200 microm in size. GME are reported to increase morbidity after cardiopulmonary bypass (CPB) and cardiac surgery. To prevent intrusion of GME into the systemic circulation during CPB, arterial line filtration is generally recommended. New trends in oxygenator design promote location of arterial filtration as an integral part of the oxygenator housing. The present experimental study aimed to evaluate the GME removal properties of an integrated arterial screen filter in a standard microporous oxygenator. The GME properties of Terumo Capiox FX25 with an integrated arterial screen filter was assessed in an experimental setup and compared with Capiox RX25, in which no arterial screen filter is present. A blood analog prime solution was recirculated using a roller pump at 4 and 6 L per minute flow rate, respectively, through a customized CPB circuit comprising oxygenator, reservoir, and connecting tubing. A controlled volume of air was introduced into the circuit. The GME activity was measured and computed using a Gampt BCC200 ultrasonic device placing one probe at the venous inlet and one other at the arterial outlet of the oxygenator. Transmembrane delta values of GME activity were used to calculate the removal efficacy based on counts and volume of GME. Use of screen filtration reduced the GME volume by 99.1% +/- .1% compared with 98.0% +/- .1% for controls at 4 L/min flow rate (p < .001). At 6 L/min, the reduction was 97.9% +/- .1% compared with 97.0% +/- .1% (p < .001). In contrast, the reduction of GME counts was less effective after screen filtration compared with controls: 89.6 +/- .6% versus 91.4 +/- .4% at 4 L/min and 55.6% +/- 1.6% versus 76.0% +/- 1.4% at 6 L/min, respectively (p < .001). The tested oxygenator with incorporated arterial screen filter reduced GME activity based on the calculated volume at the same time as counts of GME increased.

Effects of expiratory ribcage compression before endotracheal suctioning on arterial blood gases in patients receiving mechanical ventilation.

AIM AND OBJECTIVES: To investigate the effects of expiratory ribcage compression (ERCC) before endotracheal suctioning on the arterial blood gases (ABG) in patients receiving mechanical ventilation. BACKGROUND: Endotracheal suctioning is one of the most frequently used methods for airway clearance in patients receiving mechanical ventilation. Chest physiotherapy techniques such as ERCC before endotracheal suctioning can be used as a means to facilitate mobilizing and removing airway secretions and improving alveolar ventilation. DESIGN: A prospective, randomized, controlled cross-over design. METHODS: A randomized controlled cross-over trial with a convenience sample of 70 mechanically ventilated patients was conducted from 2006 to 2007. The patients received endotracheal suctioning with (experiment-period) or without (control-period) an antecedent 5-min expiratory ribcage. All the patients experienced both periods with at least a 3-h washed-out interval between the two periods. ABG were measured 5 min before and 25 min after endotracheal suctioning. RESULTS: The statistical tests showed that the levels of partial pressure of oxygen (PaO2 )/fraction of inspired oxygen (FiO2 ), partial pressure of carbon dioxide (PaCO2 ) and arterial oxygen saturation (SaO2 ) in the experimental period at 25 min after the intervention were significantly different from the control period. The tests also revealed that the levels of these variables at 25 min after suctioning were also significantly different from baseline values. However, these differences were clinically significant only for PaO2 /FiO2 . CONCLUSION: By improving the levels of PaO2 /FiO2 , ERCC can reduce the patients' need for oxygen and hence it can at least reduce the side effects of oxygen therapy. RELEVANCE TO CLINICAL PRACTICE: Improving PaO2 /FiO2 levels means less need for oxygen therapy. Hence, by applying ERCC we can at least minimize the side effects of oxygen therapy.

Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo.

Hyperoxic lung injury is a major concern in critically ill patients who receive high concentrations of oxygen to treat lung diseases. Successful abrogation of hyperoxic lung injury would have a huge impact on respiratory and critical care medicine. Hydrogen can be administered as a therapeutic medical gas. We recently demonstrated that inhaled hydrogen reduced transplant-induced lung injury and induced heme oxygenase (HO)-1. To determine whether hydrogen could reduce hyperoxic lung injury and investigate the underlying mechanisms, we randomly assigned rats to four experimental groups and administered the following gas mixtures for 60 h: 98% oxygen (hyperoxia), 2% nitrogen; 98% oxygen (hyperoxia), 2% hydrogen; 98% balanced air (normoxia), 2% nitrogen; and 98% balanced air (normoxia), 2% hydrogen. We examined lung function by blood gas analysis, extent of lung injury, and expression of HO-1. We also investigated the role of NF-E2-related factor (Nrf) 2, which regulates HO-1 expression, by examining the expression of Nrf2-dependent genes and the ability of hydrogen to reduce hyperoxic lung injury in Nrf2-deficient mice. Hydrogen treatment during exposure to hyperoxia significantly improved blood oxygenation, reduced inflammatory events, and induced HO-1 expression. Hydrogen did not mitigate hyperoxic lung injury or induce HO-1 in Nrf2-deficient mice. These findings indicate that hydrogen gas can ameliorate hyperoxic lung injury through induction of Nrf2-dependent genes, such as HO-1. The findings suggest a potentially novel and applicable solution to hyperoxic lung injury and provide new insight into the molecular mechanisms and actions of hydrogen.

Hepatic portal venous gas following colonoscopy in a patient with Crohn's disease.

Hepatic portal venous gas is a rare condition that occurs when intraluminal gas or gas produced by intestinal bacteria enters the portal venous circulation. It has recently been recognized as a rare complication of colon procedures by endoscopy or barium enema. Given the frequency of these procedures in patients with inflammatory bowel disease, hepatic portal venous gas may occur more frequently in these patients than previously reported. Here, we report a woman with Crohn's disease who developed hepatic portal venous gas following colonoscopy who was treated with conservative therapy.

Bubbles in live-stranded dolphins.

Bubbles in supersaturated tissues and blood occur in beaked whales stranded near sonar exercises, and post-mortem in dolphins bycaught at depth and then hauled to the surface. To evaluate live dolphins for bubbles, liver, kidneys, eyes and blubber-muscle interface of live-stranded and capture-release dolphins were scanned with B-mode ultrasound. Gas was identified in kidneys of 21 of 22 live-stranded dolphins and in the hepatic portal vasculature of 2 of 22. Nine then died or were euthanized and bubble presence corroborated by computer tomography and necropsy, 13 were released of which all but two did not re-strand. Bubbles were not detected in 20 live wild dolphins examined during health assessments in shallow water. Off-gassing of supersaturated blood and tissues was the most probable origin for the gas bubbles. In contrast to marine mammals repeatedly diving in the wild, stranded animals are unable to recompress by diving, and thus may retain bubbles. Since the majority of beached dolphins released did not re-strand it also suggests that minor bubble formation is tolerated and will not lead to clinically significant decompression sickness.

External ears for non-invasive and stable monitoring of volatile organic compounds in human blood.

Volatile organic compounds (VOCs) released through skin (transcutaneous gas) has been increasing in importance for the continuous and real-time assessment of diseases or metabolisms. For stable monitoring of transcutaneous gas, finding a body part with little interference on the measurement is essential. In this study, we have investigated the possibility of external ears for stable and real-time measurement of ethanol vapour by developing a monitoring system that consisted with an over-ear gas collection cell and a biochemical gas sensor (bio-sniffer). The high sensitivity with the broad dynamic range (26 ppb-554 ppm), the high selectivity to ethanol, and the capability of the continuous measurement of the monitoring system uncovered three important characteristics of external ear-derived ethanol with alcohol intake for the first time: there is little interference from sweat glands to a sensor signal at the external ear; similar temporal change in ethanol concentration to that of breath with delayed peak time (avg. 13 min); relatively high concentration of ethanol relative to other parts of a body (external ear-derived ethanol:breath ethanol = 1:590). These features indicated the suitability of external ears for non-invasive monitoring of blood VOCs.

Is hydrogen sulfide a circulating "gasotransmitter" in vertebrate blood?

Hydrogen sulfide (H(2)S) is gaining acceptance as a signaling molecule and has been shown to elicit a variety of biological effects at concentrations between 10 and 1000 micromol/l. Dissolved H(2)S is a weak acid in equilibrium with HS(-) and S(2-) and under physiological conditions these species, collectively referred to as sulfide, exist in the approximate ratio of 20% H(2)S, 80% HS(-) and 0% S(2-). Numerous analyses over the past 8 years have reported plasma or blood sulfide concentrations also in this range, typically between 30 and 300 micromol/l, thus supporting the biological studies. However, there is some question whether or not these concentrations are physiological. First, many of these values have been obtained from indirect methods using relatively harsh chemical conditions. Second, most studies conducted prior to 2000 failed to find blood sulfide in micromolar concentrations while others showed that radiolabeled (35)S-sulfide is rapidly removed from blood and that mammals have a relatively high capacity to metabolize exogenously administered sulfide. Very recent studies using H(2)S gas-sensing electrodes to directly measure sulfide in plasma or blood, or HPLC analysis of head-space gas, have also indicated that sulfide does not circulate at micromolar levels and is rapidly consumed by blood or tissues. Third, micromolar concentrations of sulfide in blood or exhaled air should be, but are not, malodorous. Fourth, estimates of dietary sulfur necessary to sustain micromolar levels of plasma sulfide greatly exceed the daily intake. Collectively, these studies imply that many of the biological effects of sulfide are only achieved at supra-physiological concentrations and they question whether circulating sulfide is a physiologically relevant signaling molecule. This review examines the blood/plasma sulfide measurements that have been reported over the past 30 years from the perspective of the analytical methods used and the potential sources of error.