Peak Carboxyhemoglobin Levels Research Articles

Carboxyhemoglobin in Cardiac Surgery Patients and Its Association with Risk Factors and Biomarkers of Hemolysis.

Cardiac surgery with cardiopulmonary bypass (CPB) is associated with hemolysis. Yet, there is no easily available and frequently measured marker to monitor this hemolysis. However, carboxyhemoglobin (CO-Hb), formed by the binding of carbon monoxide (a product of heme breakdown) to hemoglobin, may reflect such hemolysis. We hypothesized that CO-Hb might increase after cardiac surgery and show associations with operative risk factors and indirect markers for hemolysis. We conducted a retrospective descriptive cohort study of data from on-pump cardiac surgery patients. We analyzed temporal changes in CO-Hb levels and applied a generalized linear model to assess patient characteristics associated with peak CO-Hb levels. Additionally, we examined their relationship with red blood cell (RBC) transfusion and bilirubin levels. We studied 38,487 CO-Hb measurements in 1735 patients. CO-Hb levels increased significantly after cardiac surgery, reaching a peak CO-Hb level 2.1 times higher than baseline ( P < .001) at a median of 17 hours after the initiation of surgery. Several factors were independently associated with higher peak CO-Hb, including age ( P < .001), preoperative respiratory disease ( P = .001), New York Heart Association Class IV ( P = .019), the number of packed RBC transfused ( P < .001), and the duration of CPB ( P = .002). Peak CO-Hb levels also significantly correlated with postoperative total bilirubin levels (Rho = 0.27, P < .001). CO-Hb may represent a readily obtainable and frequently measured biomarker that has a moderate association with known biomarkers of and risk factors for hemolysis in on-pump cardiac surgery patients. These findings have potential clinical implications and warrant further investigation.

Carboxyhemoglobin levels in children during extracorporeal membrane oxygenation support: a retrospective study.

Hemolysis is a common complication of extracorporeal membrane oxygenation (ECMO). There are few data on whether carboxyhemoglobin (COHb), a potential marker of hemolysis, are elevated during ECMO support. We conducted a single-center, retrospective study comparing peak COHb levels of children pre-, during, and post-ECMO from January 2017 to August 2020. There were 154 ECMO runs in 147 children (154 PICU admissions) included in the study. The median age was 3.5 (IQR 0.2, 39.2) months. Veno-arterial ECMO was the predominant mode: 146/154 (94.8%). Eighty-seven children (56.5%) underwent cardiac surgery. Peak COHb levels during ECMO were statistically significantly higher compared to pre ECMO (COHb 1.8% (IQR 1.4, 2.6) vs COHb 1.2% (IQR 0.7, 1.7), p < 0.001) and post ECMO (COHb 1.6% (IQR 1.3, 2.2), p = 0.009). Children with COHb ⩾2% were younger and had longer duration of ECMO support. Plasma hemoglobin weakly correlated with COHb level (r = 0.14; p = 0.04). Carboxyhemoglobin levels increased during ECMO support compared to the pre and post ECMO period. Younger age and longer ECMO duration were associated with COHb levels ⩾2%. Plasma hemoglobin weakly correlated with COHb level.

Analysis of factors that influence rates of carbon monoxide uptake, distribution, and washout from blood and extravascular tissues using a multicompartment model

To better understand factors that influence carbon monoxide (CO) washout rates, we utilized a multicompartment mathematical model to predict rates of CO uptake, distribution in vascular and extravascular (muscle vs. other soft tissue) compartments, and washout over a range of exposure and washout conditions with varied subject-specific parameters. We fitted this model to experimental data from 15 human subjects, for whom subject-specific parameters were known, multiple washout carboxyhemoglobin (COHb) levels were available, and CO exposure conditions were identical, to investigate the contributions of exposure conditions and individual variability to CO washout from blood. We found that CO washout from venous blood was biphasic and that postexposure times at which COHb samples were obtained significantly influenced the calculated CO half times (P < 0.0001). The first, more rapid, phase of CO washout from the blood reflected the loss of CO to the expired air and to a slow uptake by the muscle compartment, whereas the second, slower washout phase was attributable to CO flow from the muscle compartment back to the blood and removal from blood via the expired air. When the model was used to predict the effects of varying exposure conditions for these subjects, the CO exposure duration, concentration, peak COHb levels, and subject-specific parameters each influenced washout half times. Blood volume divided by ventilation correlated better with half-time predictions than did cardiac output, muscle mass, or ventilation, but it explained only approximately 50% of half-time variability. Thus exposure conditions, COHb sampling times, and individual parameters should be considered when estimating CO washout rates for poisoning victims.

Role of glutathione in metabolic degradation of dichloromethane in rats

Dichloromethane (DCM) elimination and carboxyhemoglobin (COHb) generation were examined in adult female SD rats pretreated with a glutathione (GSH) depletor(s). Rats were treated with either buthionine sulfoximine (BSO; 2 mmol/kg, i.p.), diethylmaleate (DEM; 3 mmol/kg, i.p.), phorone (PHO; 1 mmol/kg, i.p.) or BSO plus PHO (BSO; 2 mmol/kg +PHO; 0.5 mmol/kg, i.p.). The hepatic GSH concentration was significantly reduced by each treatment. Decrease in hepatic GSH was maintained at least for 10 h after BSO treatment but recovered rapidly in rats treated with DEM or PHO. The hepatic p-nitrophenol hydroxylase activity was not affected by the GSH depletors at the dose used in this study. Rats were treated with an i.p. injection of DCM (3 mmol/kg) and the concentrations of DCM and the COHb levels in blood were monitored. In rats pretreated with a GSH depletor, the peak COHb level was significantly greater than that of rats treated with DCM only. The peak COHb level attained in each group of rats appeared to be inversely related to the magnitude of reduction in hepatic GSH levels. The half-life of DCM in blood was also increased in rats pretreated with the GSH depletor(s). The results indicate that the GSH-dependent metabolic reaction has an important role in the overall elimination of DCM as well as in the metabolic generation of carbon monoxide (CO) from this solvent.

Anesthesia-associated carbon monoxide exposures among surgical patients.

To estimate the extent of, and evaluate risk factors for, elevated carboxyhemoglobin levels among patients undergoing general anesthesia and to identify the source of carbon monoxide. Matched case-control study to measure carboxyhemoglobin levels. Large academic medical center. 45 surgical patients who underwent general anesthesia Case-patients were more likely than controls to undergo surgery on Monday or Tuesday (10/15 vs 7/30; matched odds ratio [mOR], 7.7; 95% confidence interval [CI95], 1.8-34; P=.01), in one particular room (7/15 vs 4/30; mOR, 8.5; CI95, 1.5-48; P=.03) or in a room that was idle for > or =24 hours (11/15 vs 1/30; mOR, 95.5; CI95, 8.0-1,138; P< or =.001). In a multivariate model, only rooms, and hence the anesthesia equipment, that were idle for > or =24 hours were independently associated with elevated intraoperative carboxyhemoglobin levels (OR, 22.4; CI95, 1.5-338; P=.025). Moreover, peak carboxyhemoglobin levels were correlated with the length of time that the room was idle (r=0.7; CI95, 0.3-0.9). Carbon monoxide was detected in the anesthesia machine outflow during one case-procedure. No contamination of anesthesia gas supplies or CO2 absorbents was found. Carbon monoxide may accumulate in anesthesia circuits left idle for > or =24 hours as a result of a chemical interaction between CO2-absorbent granules and anesthetic gases. Patients administered anesthesia through such circuits may be at increased risk for elevated carboxyhemoglobin levels during surgery or the early postoperative period.

Increased lipid peroxidation and decreased antioxidant activity correspond with death after smoke exposure in the rat.

Oxidants are released directly from smoke and also as a result of the airways inflammation that occurs after smoke injury. We determined the relation between the degree of tissue oxidant change with the use of malondialdehyde content to measure lipid peroxidation and the degree of lung and systemic organ damage and resulting damage mortality 24 hours after a controlled smoke exposure in a rat model. We also monitored changes in the key tissue antioxidant catalase. We found that the degree of lung lipid peroxidation and the decrease in catalase activity directly correlated with mortality caused by respiratory failure and with the degree of lung inflammation but that they did not correlate with the peak carboxyhemoglobin level, a marker of smoke gas phase exposure. The lung oxidant changes also directly correlated with increased systemic lipid peroxidation and decreased catalase in liver and kidney tissue. We conclude that the initial smoke insult causes lung and in turn systemic inflammation with resulting release of oxidants, which leads to tissue oxidant injury. The degree of lung oxidant change significantly correlates with the degree of lung tissue injury, respiratory failure, and mortality, and the major source of the oxidant changes is tissue inflammation rather than oxidants in the smoke itself.

Smoke inhalation injury in sheep is caused by the particle phase, not the gas phase

The inhalation of smoke can produce severe lung injury, particularly to airways. We assessed the role of the toxic compounds in the particle phase vs. those in the gas phase of smoke in the injury process by filtering out all particles > 0.3 micron diam before exposure. Adult sheep (n = 16) were insufflated with a well-characterized cellulose smoke. Mean particle size was 3 +/- 0.4 micron diam. A standardized dose of 12 breaths of whole or filtered smoke (n = 8/group) was given to sheep under anesthesia with a tidal volume of 20 ml/kg. Sheep were awakened and monitored for 24 h and then killed. Peak carboxyhemoglobin levels were 40-45% in both groups. Severe respiratory failure occurred only in the whole-smoke group, as evidenced by an increase in shunt fraction from a control of 0.04 +/- 0.02 to 0.28 +/- 0.05, a decrease in lung compliance of 50%, and histological evidence of severe airway mucosal edema, ulceration, and bronchorrhea. No significant physiological, histological, or biochemical changes were noted in the filtered-smoke group.

Effect of increasing the tidal volume of smoke breaths on smoke-induced lung dysfunction

We determined the effect of a graded increase in lung exposure to a toxic smoke by increasing smoke tidal volume (VT) or the number of smoke breaths. Sheep were anesthetized and then insufflated with cooled cotton toweling smoke; VT was 5, 10, or 20 ml/kg, and smoke breaths were varied from 12 to 48. The smoke had a uniform particle size (3 +/- 0.4 microns diam). Peak carboxyhemoglobin levels varied from 8 +/- 2 to 45 +/- 4% in the lowest to highest exposure groups, respectively. Animals were monitored unanesthetized for 24 h, and then they were killed. Oxygenation (ratio of arterial PO2 to fraction of inspire O2) decreased from 480 +/- 21 to 200 Torr, and compliance decreased by approximately 50% in the highest smoke exposure groups, whereas only a modest decrease in oxygenation and no compliance changes were seen with lesser exposures. A moderate tracheobronchitis, some atelectasis, and no alveolar edema were noted in the lower smoke exposure groups, whereas severe tracheobronchitis, airway edema, and alveolar atelectasis were observed in the highest exposure group. Only modest alveolar flooding was noted. Impaired oxygenation and anatomic injury correlated best with the total smoke delivered (r = 0.59). Increasing VT from 5 to 20 ml/kg did not increase airway or alveolar injury if the total smoke mass delivered was maintained constant. The degree of impaired oxygenation did not correlate with measured lung water (r = 0.27) or lung lymph flow (r = 0.31).

Methylene iodide poisoning

A 20-month-old girl ingested a maximum of 25 mL of pure methylene iodide. Within two hours, the patient exhibited lethargy and incoordination and vomited. An abdominal radiograph demonstrated the radiopaque material in the gut. In vivo conversion to carbon monoxide was documented with a peak carboxyhemoglobin level of 14.2% reached at 11 hours after ingestion. Two days after ingestion, evidence of hepatotoxicity was apparent, and fulminant hepatic failure quickly ensued. Despite aggressive supportive care and transfer to a liver transplant center, the patient died nine days after ingestion. Methylene iodide ingestion has not been previously reported in human beings. This case verifies that this substance is a potent hepatotoxin, is metabolized to carbon monoxide in vivo, is radiopaque, and may cause bone marrow suppression.

Complications and protocol considerations in carbon monoxide-poisoned patients who require hyperbaric oxygen therapy: report from a ten-year experience.

We conducted a study to determine the type, incidence, and timing of complications that occur in patients who have a carbon monoxide (CO) exposure serious enough to require hyperbaric oxygen therapy (HBOT). Complication data were retrospectively collected from a ten-year period for 297 consecutive CO-poisoned emergency department patients who received HBOT. HBOT was indicated for 41% of the patients because of an elevated carboxyhemoglobin (COHb) level alone. Central nervous system dysfunction, including loss of consciousness, and/or cardiovascular dysfunction, was the criteria for HBOT in 59% of patients, regardless of their COHb level. The mean peak COHb level was 38 mg%, with 88% of patients having a peak COHb level greater than 25 mg%. The mortality rate was 6% in this case series. Cardiac arrest occurred in 8% of patients; all experienced their first arrest prior to HBOT. The 3% of patients who sustained an isolated respiratory arrest and those who had a myocardial infarction did so prior to HBOT. Several complications, however, occurred for the first time or as a recurrent event during HBOT. These included emesis (6%), seizures (5%), agitation requiring restraints or sedation (2%), cardiac dysrhythmias or arrests (2%), and arterial hypotension (2%). No patient's level of consciousness deteriorated subsequent to the initial resuscitation except for those who later had a generalized seizure. The most significant complication attributable to HBOT was tension pneumothorax, noted in three patients (1%).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary responses after spontaneous inhalation of Douglas fir smoke in goats.

In the majority of clinical cases, smoke inhalation results in a self-limited lung injury mostly confined to the airways. In this study, an animal model of inhalation injury was developed that reflected similar pathophysiology. Cardiopulmonary parameters were studied in awake, instrumented goats following spontaneous inhalation of characterized Douglas fir smoke. Peak carboxyhemoglobin levels averaged 37% during a mean exposure time of 33 minutes. All animals survived the 24-hour study period, and showed only transient abnormalities in lung fluid balance and gas exchange, with no change in lung mechanics or plasma eicosanoid (TxB2 and 6-keto-PGF1 alpha) levels. However, extravascular lung water at 24 hours was increased 33%, suggesting the presence of some airway edema and retained secretions. We feel this model fairly represents the majority of clinical smoke inhalation cases. This model is compared to other large animal inhalation injury models producing more severe lung injury.

Myocardial effects of long-term cigarette smoking: Relative roles of carbon monoxide and nicotine

In a prior study of an animal model exposed to long-term cigarette smoking, left ventricular performance was observed to decline in association with morphologic evidence of collagen accumulation. Because controversy has existed as to whether nicotine or carbon monoxide is the major pathogenetic agent in cigarette smoking, 18 young adult male beagles with chronic tracheostomy were placed in three groups of six dogs each: Group 1 served as a control group; group 2 received seven cigarettes of low nicotine content (0.2 mg/cigarette), which effected a peak carboxyhemoglobin level approximating 5/100 ml, similar to that of regular cigarettes; and group 3 received nicotine twice daily intramuscularly in an amount equivalent to seven cigarettes/day. In the intact anesthetized state, heart rate, left ventricular end-diastolic pressure and volume (indicator dilution) did not differ among the three groups. To assess relative myocardial wall stiffness, saline solution was infused into the left ventricular chamber. A significantly higher end-diastolic pressure and tension were elicited in group 3, suggesting a decrease in left ventricular compliance. No such change was observed in either group 1 or 2. Only long-term nicotine use was associated with increased hydroxyproline content in the left ventricular myocardium, suggesting a basis for enhanced stiffness. An index of left ventricular contractility was derived from the peak rate of rise of left ventricular pressure ( dP dt ), normalized for preload and afterload. Groups 1 and 2 showed no difference in this index (2.18 ± 0.3 versus 2.15 ± 0.18 muscle lengths/s per cm) at similar levels of aortic pressure, but the index was significantly lower (1.28 ± 0.12, p < 0.01) in group 3. Thus, the effects of long-term cigarette use on the myocardium appear to be predominantly dependent on nicotine rather than on carbon monoxide.