Kevin R. Hardy

Delayed Neuropsychologic Sequelae After Carbon Monoxide Poisoning: Prevention by Treatment With Hyperbaric Oxygen

STUDY OBJECTIVE Carbon monoxide (CO) poisoning is a major clinical problem. The risk of morbidity and the most effective treatment have not been clearly established. We measured the incidence of delayed neurologic sequelae (DNS) in a group of patients acutely poisoned with CO and tested the null hypothesis that the incidence would not be affected by treatment with hyperbaric oxygen (HBO). DESIGN We conducted a prospective, randomized study in patients with mild to moderate CO poisoning who presented within 6 hours. Patients had no history of loss of consciousness or cardiac instability. INTERVENTIONS The incidence of DNS was compared between groups treated with ambient pressure 100% oxygen or HBO (2.8 ATA for 30 minutes followed by 2.0 ATA oxygen for 90 minutes). DNS were defined as development of new symptoms after oxygen treatment plus deterioration on one or more subtests of a standardized neuropsychologic screening battery. RESULTS In 7 of 30 patients (23%), DNS developed after treatment with ambient-pressure oxygen, whereas no sequelae developed in 30 patients after HBO treatment (P < .05). DNS occurred 6 +/- 1 (mean +/- SE) days after poisoning and persisted 41 +/- 8 days. At follow-up 4 weeks after poisoning, patients who had been treated with ambient pressure oxygen and had not sustained DNS exhibited a worse mean score on one subtest, Trail Making, compared with the group treated with HBO and with a control group matched according to age and education level. There were no differences in scores between the control group and the hyperbaric oxygen group. CONCLUSION DNS after CO poisoning cannot be predicted on the basis of a patients clinical history or CO level. HBO treatment decreased the incidence of DNS after CO poisoning.

Pathophysiology and treatment of carbon monoxide poisoning.

Carbon monoxide poisoning is the leading cause of poisoning deaths in the US, and published reports of carbon monoxide related morbidity and mortality can vary widely. Common morbidity involves myocardial and/or neurologic injury including delayed neurologic sequelae. The pathophysiology of this entity is complex, involving hypoxic stress on the basis of interference with oxygen transport to the cells and possibly impairing electron transport. Carbon monoxide can also affect leukocytes, platelets and the endothelium, inducing a cascade of effects resulting in oxidative injury. Carboxyhemoglobin levels are valuable for confirming carbon monoxide exposure but cannot be used to stratify severity of poisoning, predict prognosis, or indicate a specific treatment plan. Oxygen therapy is the key treatment of carbon monoxide intoxication, and hyperbaric oxygen has been shown to interdict and improve clinical outcome in some patients. Immediate treatment with a high fraction of inspired oxygen and careful clinical evaluation are mandatory. Timely referral for hyperbaric oxygen is indicated for patients with any history of unconsciousness, cardiovascular instability or ischemia, and persistent mental and/or neurologic deficits. Hyperbaric oxygen should also be considered in certain other patient subsets.

Plasma biomarkers in carbon monoxide poisoning.

Objectives. The severity of acute carbon monoxide (CO) poisoning is often based on non-specific clinical criteria because there are no reliable laboratory markers. We hypothesized that a pattern of plasma protein values might objectively discern CO poisoning severity. This was a pilot study to evaluate protein profiles in plasma samples collected from patients at the time of initial hospital evaluation. The goal was to assess whether any values differed from age- and sex-matched controls using a commercially available plasma screening package. Methods. Frozen samples from 63 suspected CO poisoning patients categorized based on clinical signs, symptoms, and blood carboxyhemoglobin level were analyzed along with 42 age- and sex-matched controls using Luminex-based technology to determine the concentration of 180 proteins. Results. Significant differences from control values were found for 99 proteins in at least one of five CO poisoning groups. A complex pattern of elevations in acute phase reactants and proteins associated with inflammatory responses including chemokines/cytokines and interleukins, growth factors, hormones, and an array of auto-antibodies was found. Fourteen protein values were significantly different from control in all CO groups, including patients with nominal carboxyhemoglobin elevations and relatively brief intervals of exposure. Conclusions. The data demonstrate the complexity of CO pathophysiology and support a view that exposure causes acute inflammatory events in humans. This pilot study has insufficient power to discern reliable differences among patients who develop neurological sequelae but future trials are warranted to determine whether plasma profiles predict mortality and morbidity risks of CO poisoning.

CD34+/CD45-dim stem cell mobilization by hyperbaric oxygen — Changes with oxygen dosage☆

Because hyperbaric oxygen treatment mobilizes bone marrow derived-stem/progenitor cells by a free radical mediated mechanism, we hypothesized that there may be differences in mobilization efficiency based on exposure to different oxygen partial pressures. Blood from twenty consecutive patients was obtained before and after the 1st, 10th and 20th treatment at two clinical centers using protocols involving exposures to oxygen at either 2.0 or 2.5 atmospheres absolute (ATA). Post-treatment values of CD34+, CD45-dim leukocytes were always 2-fold greater than the pre-treatment values for both protocols. Values for those treated at 2.5 ATA were significantly greater than those treated at 2.0 ATA by factors of 1.9 to 3-fold after the 10th and before and after the 20th treatments. Intracellular content of hypoxia inducible factors -1, -2, and -3, thioredoxin-1 and poly-ADP-ribose polymerase assessed in permeabilized CD34+ cells with fluorophore-conjugated antibodies were twice as high in all post- versus pre-treatment samples with no significant differences between 2.0 and 2.5 ATA protocols. We conclude that putative progenitor cell mobilization is higher with 2.5 versus 2.0 ATA treatments, and all newly mobilized cells exhibit higher concentrations of an array of regulatory proteins.

A preliminary study in the alterations of mitochondrial respiration in patients with carbon monoxide poisoning measured in blood cells

Abstract Objectives: Carbon monoxide (CO) is a colorless and odorless gas responsible for poisoning mortality and morbidity in the United States. At this time, there is no reliable method to predict the severity of poisoning or clinical prognosis following CO exposure. Whole blood cells, such as peripheral blood mononuclear cells (PBMCs) and platelets, have been explored for their potential use to act as sensitive biomarkers for mitochondrial dysfunction which may have a role in CO poisoning. Design: The objective of this study was to measure mitochondrial respiration using intact cells obtained from patients exposed to CO as a potential biomarker for mitochondrial inhibition with results that can be obtained in a time frame useful for guiding clinical care. This was a prospective, observational pilot study performed from July 2015 to July 2016 at a single academic tertiary care center that is the location of the region’s only multi chamber hyperbaric. Measurements: Clinical characteristics, patient demographics, mitochondrial respiration and outcomes were recorded. Main results: There were 7 patients enrolled with a mean COHb level 26.8 ± 10 and with a mean lactate of 1.1 ± 0.4 mmol/L. All 7 CO exposures were related to heat generators used during winter months with two deaths. There was a positive correlation between maximal respiration and COHb levels with both high maximal respiration and high spare respiratory capacity correlating with a high COHb level. There was a subset of PBMCs (n = 4) that were analyzed for Complex IV (cytochrome c oxidase) activity. Conclusions: In this pilot study, measurements can be performed in an appropriate timeline for clinical care with potential to serve as a prognostic marker. Further work is necessary to develop high-resolution respirometry as a clinical tool for assessing the severity of illness and guiding therapy.