Roy A. M. Myers

Subacute sequelae of carbon monoxide poisoning

From January 1980 to August 1983, 213 patients with carbon monoxide poisoning were seen; 131 received hyperbaric oxygen and had no sequelae. Eighty-two patients were treated with normobaric oxygen; ten (12.1%) returned with clinically significant sequelae. The specific neurological sequelae included headaches, irritability, personality changes, confusion, and loss of memory. This recurrent symptomatology developed within one to 21 days (mean, 5.7 days) after the initial exposure, although no reexposure occurred. These recurring symptoms resolved rapidly with hyperbaric oxygen therapy. We recommend that hyperbaric oxygen therapy be used whenever CO poisoning symptoms recur.

A neuropsychological screening battery for emergency assessment of carbon-monoxide-poisoned patients.

The Carbon Monoxide Neuropsychological Screening Battery (CONSB) was developed to improve the neurological assessment of CO-poisoned patients in an emergency setting. Traditional assessment methods (clinical examination and carboxyhemoglobin [CoHb] levels) readily can identify unconscious, severely involved patients; however, many CO-intoxicated patients with cerebral impairment who also require aggressive hyperbaric oxygen therapy are assessed inadequately by such methods. Administration of the CONSB to 66 CO-poisoned patients and 66 volunteer controls revealed significant differences in performance between the two groups. It was concluded that the CONSB enhanced the accuracy of the evaluation of cerebrally impaired CO-poisoned patients. Failure to assess the cerebral functioning of patients exposed to CO and to identify those who require aggressive oxygen therapy could have neurological sequelae.

Hyperoxia prolongs the aminoglycoside-induced postantibiotic effect in Pseudomonas aeruginosa.

The objective of this study was to determine whether hyperoxia enhances aminoglycoside activity against Pseudomonas aeruginosa. The existence of tobramycin-oxygen synergy was determined by using the in vitro postantibiotic effect (PAE). P. aeruginosa strains were incubated for 1 h in medium containing tobramycin at four times the MIC in the following gas mixtures: normoxia (21% O2), hyperoxia (100% O2, 101.3 kPa), or hyperbaric oxygen (100% O2, 274.5 kPa). Tobramycin was removed after 1 h and bacteria were incubated under normoxic conditions; growth rates were measured for 5 h. Exposure of three P. aeruginosa strains to hyperoxia prolonged the PAE of tobramycin approximately twofold compared with the PAE after exposure to normoxia (P less than 0.05). Exposure of P. aeruginosa ATCC 27853 to tobramycin and hyperbaric oxygen prolonged the time required for bacteria to increase 1 log10 CFU/ml compared with the time after exposure for this increase to occur in tobramycin-treated, normoxic or hyperoxic groups (P less than 0.02). Pulse-chase labeling of bacteria with L-[35S]methionine, immediately after removal of tobramycin, showed that protein synthesis rates were decreased compared with those in controls (P = 0.0001). Moreover, in tobramycin-treated groups, hyperoxia and hyperbaric oxygen induced 2- and 16-fold decreases, respectively, in protein synthesis rates compared with normoxia; these results did not achieve statistical significance. In the absence of tobramycin, hyperoxia increased bacterial growth (134%; P less than 0.01) and protein synthesis (24%; not significant) compared with normoxia. Hyperbaric oxygen, however, delayed the growth recovery of bacteria (P less than 0.05). We conclude that hyperoxia enhances the bacteriostatic effects of tobramycin in a synergistic manner.+

Functional and structural evaluation of the vasculature of skin flaps after ischemia and reperfusion.

Free radicals and other toxic oxygen species play a role in the pathogenesis of ischemic organ damage. The abdominal skin flap has been used as a model to study the effects of superoxide dismutase on the survival of ischemic skin. We have evaluated the evolution of functional and structural injury to the vasculaturc after ischemic injury in superoxide dismutase-treated and control skin flaps. Ischemia was induced by creating abdominal skin flaps and occluding either the venous or both the venous and arterial blood supplies. Superoxide dismutase was administered immediately after the occlusion was released. At 1 hour of reflow, erythrocyte stasis, platelet deposition, neutrophil adherence, and injury to the endothelium of the large vessels and of the microvas-culature were evident. The blood flow in the ischemic skin was only 3 percent of normal. Superoxide dismutase caused no change in the ultrastructure of the vasculature and a marginal decrease in vascular permeability in the ischemic skin at 1 hour of reflow. Increased fluorescent staining of the skin was evident after 24 hours of reflow in the superoxide dismutase-treated flaps. These findings indicate that injury to vascular endothelium by ischemia and reperfusion plays a role in the evolution of skin necrosis.

Confirmation of the Pulse Oximetry Gap in Carbon Monoxide Poisoning

STUDY OBJECTIVES To demonstrate the degree to which pulse oximetry overestimates actual oxyhemoglobin (O2Hb) saturation in patients with carbon monoxide (CO) poisoning. This phenomenon has been reported in fewer than 20 humans in the English medical literature. METHODS A retrospective chart review of 191 patients evaluated for CO poisoning at a regional hyperbaric center identified 124 patients 10 years of age and older who had had both arterial blood gas and pulse oximetry measurements and who had received either high-flow oxygen through a nonrebreather mask or 100% inspired oxygen through an endotracheal tube. Blood gas measurements, including direct spectrophotometric determination of O2Hb and carboxyhemoglobin (COHb) saturation values, were compared with finger-probe pulse oximetry readings. RESULTS Measured O2Hb saturation (mean +/- SD, 88.7 +/- 10.2%; range, 51.4% to 99.0%) decreased linearly and predictably with rising COHb levels (10.7 +/- 10.4%; range, .2% to 46.4%). Pulse oximetry saturation (99.2% +/- 1.3%; range, 92% to 100%) remained elevated across the range of COHb levels and failed to detect decreased O2Hb saturation. The pulse oximetry gap, defined as the difference between pulse oximetry saturation and actual O2Hb saturation (10.5% +/- 9.7%; range, 0% to 40.6%), approximated the COHb level. CONCLUSION There is a linear decline in O2Hb saturation as COHb saturation increases. This decline is not detected by pulse oximetry, which therefore overestimates O2Hb saturation in patients with increased COHb levels. The pulse oximetry gap increases with higher levels of COHb and approximates the COHb level. In patients with possible CO poisoning, pulse oximetry must be considered unreliable and interpreted with caution until the COHb level has been measured.

Are arterial blood gases of value in treatment decisions for carbon monoxide poisoning

Traditionally, the carboxyhemoglobin (HbCO) level has been used to estimate the severity of carbon monoxide (CO) poisoning. Through extensive clinical experience, we have found this to be an inaccurate correlation; thus, other variables such as pHa or psychometric abnormalities have been assessed to determine severity from CO poisoning. In a 5-yr experience with 247 patients, on admission 114 had an arterial blood gas and HbCO determinations, and 88 also had psychometric testing. The data were evaluated to determine any relationship between pH and HbCO level; a weak correlation (r approximately equal to -0.3) was discovered. A comparison of psychometric testing with HbCO level showed a much stronger statistical relationship. The definition of HbCO poisoning severity may be better determined by psychometric testing than by the HbCO level because psychometric testing measures actual neurologic disability. The weak correlation between both psychometric testing and the HbCO level with pHa reinforces the clinical impression that patients with acidosis, alkalosis, or normal blood gases could have equally severe neurologic symptomatology at HbCO levels ranging from 1% to 62%.

Hyperbaric oxygen treatment for experimental cyclophosphamide-induced hemorrhagic cystitis

Acrolein is a toxic metabolite of cyclophosphamide that causes hemorrhagic cystitis in 2 to 40% of treated patients. Hyperbaric oxygen (HBO) is used to treat poorly healing wounds in conditions such as Fourniers gangrene and radiation-induced cystitis. The present study was designed to evaluate the effects of HBO on acute acrolein-induced hemorrhagic cystitis in a rat model. Rats were divided into 4 groups. Group I served as a control and received only HBO prior to sacrifice. Group II received acrolein only, while groups III and IV received acrolein as well as HBO therapy. Hyperbaric oxygen (100% oxygen, 2.8 atmospheres, 90 minutes) was delivered twice a day for 4 days, with group III receiving a fifth HBO treatment just before acrolein and group IV receiving the fifth HBO treatment just after acrolein. After therapy, the amount of urothelial injury was determined morphometrically. Group II untreated rat bladders had only 33% of the urothelium intact after acrolein injury, whereas groups III and IV rat bladders had 93% (p < 0.01) and 55% (p < 0.01) intact urothelium, respectively, after treatment with HBO. The timing of the HBO treatment appeared to be a critical factor, with less injury occurring if the fifth HBO treatment immediately preceded acrolein. These results suggest that HBO may be useful as prophylaxis and treatment of cyclophosphamide-induced hemorrhagic cystitis.

Hypothermia'. Quantitative Aspects of Therapy

Quantitative aspects of various methods of warming are presented comparing the peripheral method of warm bath immersion to the central method of ventilation with heated water-saturated air, infusion of warmed intravenous solutions, peritoneal lavage with warmed solutions, and hemodialysis or cardiopulmonary bypass. The need to convert arterial blood gas results for body temperature is emphasized. Two cases demonstrate combined use of peripheral warming using warming mattress and blankets and central warming with ventilation and infusion.

Regulation of protein degradation in normal and transformed human bronchial epithelial cells in culture

Protein degradation rates are decreased in some transformed cells of mesenchymal origin. We have tested the generality of this phenomenon and evaluated the role of the lysosomes in this down-regulation. To this end we have compared the induction of lysosomal protein degradation among normal, transformed (BEAS-2B), and transformed tumorigenic (BZR, Calu-1) human bronchial epithelial cells in culture. Serum and/or nutrient deprivation, cell confluency, and Ca2+ were used to modulate lysosomal protein degradation. Protein degradation and synthesis were determined by the release or incorporation of [14C]valine in the cells. Autophagic degradation of cytoplasm by lysosomes was evaluated by ultrastructural morphometry. Basal protein degradation was lower (27%) in two of the transformed cell lines (BEAS-2B and BZR). Incorporation of [14C]valine label was raised approximately 4-fold in the transformed cells. Nutrient deprivation stimulated protein degradation equally (2-fold) in transformed and normal cells. Postconfluency increased (1.5-fold) basal protein degradation in Calu-1 cells and a marked enhancement (4-fold) of degradation occurred during nutrient deprivation. Culture of normal human bronchial epithelial cells in high Ca2+ caused phenotypic changes and increased (30%) the degradation of protein induced by nutrient deprivation. In Calu-1, high Ca2+ caused only phenotypic changes. The volume density (Vd) of autophagic vacuoles and dense bodies in the transformed cells was lower under basal conditions but increased markedly during nutrient deprivation. A marked accumulation of lysosomes also occurred in transformed cells during postconfluency. We conclude that cell transformation lowers basal protein degradation in some human epithelial cells. Lysosomal proteolysis of transformed cells is not down-regulated and can be markedly enhanced during nutritional deprivation by the autophagic degradation pathway.

Protection of Hepatocytes with Hyperoxia against Carbon Tetrachloride-induced Injury

Hyperbaric oxygen (HPO) was administered to rats (100% O2 at 2.8 atm for 90 min) immediately or 1 hr after severe carbon tetrachloride (CCl4) intoxication in order to study the mechanisms of protection against hepatocellular injury by hyperoxia. Slight to moderate hepatocellular injury was observed, particularly by morphologic criteria, 4 hr after CCl4 intoxication. Little cell death was observed; 24 hr after CCl4, 20% of the untreated animals died. In the survivors, the following typical changes occurred in the liver: extensive hepatocellular swelling, vacuolization and necrosis; severe ultrastructural alterations; binding of CCl4 to microsomal lipids; elevation of lipid peroxidation products (conjugated dienes); little decrease in cytochrome b5 and severe decrease in cytochrome P-450 levels. Serum (ransaminase (alanine aminotransferase and aspar-tate aminotransferase) levels were elevated. Immediate treatment with HPO prevented the mortality and markedly decreased the hepatocellular necrosis 24 hr after intoxication. Immediate HPO treatment did not lower the levels of free CCl4 in the liver. However, the rise in lipid peroxidation products caused by CCl4 intoxication at 4 hr was reduced. Delayed treatment with HPO (1 hr after CCl4) prevented the mortality but was less effective in preventing necrosis. Some hepatocellular protection was still demonstrable. In particular, the rise in lipid peroxidation products was reduced. Hyperoxia protects hepatocytes against CCl4 toxicity. The rapid decline in protective effect within 60 min of intoxication suggests that hyperoxia inhibits CCl4 activation and/or damage from molecular intermediates. Hyperoxia has little effect on the progression of sublethal injury to cell death in the livers of CCl4-intoxicated rats.