Inadequacy of Pulse Oximetry in the Catheterization Laboratory. An Exploratory Study Monitoring Respiratory Status Using Arterial Blood Gases during Cardiac Catheterization with Conscious Sedation.

BACKGROUND: Benzodiazepines and opioids are commonly used for conscious sedation (CS) in cardiac catheterization laboratory (CCL) patients. Both drugs are known to predispose to hypoxemia, apnea and decreased responsiveness to PCO2, resulting in decreased arterial pH and PO2, as well as increased PCO2. We want to determine the effects of CS on arterial blood gas (ABG) in CCL patient, and identify if pulse oximetry monitoring is adequate. METHODS: We enrolled 18 subjects undergoing elective catheterization. Measurement of ABGs at one-minute intervals was done from the moment of arterial access until case end. The results of ABGs were not available to the clinician who administered sedation. Relationships of pH, PCO2, PaO2 and SaO2 were studied by plotting time series graphs. Significant changes were defined as pH <7.30, SaO2 < 90, and PCO2 > 50 mmHg. RESULTS: No significant change in pH, PCO2, PaO2 and SaO2 was noted in 4/18 (22%) subjects. A significant drop in SaO2 was noted in 4/18 (22%). A significant change in PCO2 and/or pH was noted in 10/18 (55%) cases. Among the 16 (16/18) subjects receiving supplemental oxygen, 7 (7/18, 39%) had no drop in SaO2, but developed respiratory acidosis. At the end of the case, 5/18 (28%) subjects had respiratory acidosis with normal PaO2. CONCLUSION: Significant hypercarbia and acidosis occurred frequently in this small study during CS in patients undergoing cardiac catheterization. Relying on pulse oximetry alone especially with patients on supplemental oxygen may lead to failure in detecting respiratory acidosis in a significant number of patients.

3-MeO-PCP intoxication in two young men: First in vivo detection in Italy.

3-MeO-PCP or 3-methoxyphencyclidine is a derivative of phencyclidine. It acts as a dissociative anesthetic and it has allegedly hallucinogenic and sedative effects. There are almost no documented intoxication cases and references about its pharmacology and toxicity in literature. This study presents two concomitant intoxication cases due to consumption of 3-MeO-PCP and alcohol. A 19 (A) and a 21 years old (B) men were brought to Santa Maria Nuova Hospital in a comatose state (Glasgow score 3). They showed respiratory acidosis, right anisocoria with mydriatic pupils and hypothermia. Toxicological screening was negative. They were intubated for 7-8h. Almost 24h after hospitalization they were still in a delirious and agitated status. The subjects declared a high alcohol consumption and ingestion of unknown pills. Blood and urine were collected upon their arrival to the Emergency Department and sent to our Forensic Toxicology Division. Blood alcohol content was 2.0g/L for subject A and 1,7g/L for subject B. The specimens were analyzed by means of GC-MS, revealing the presence of 3-MeO-PCP. A confirmation and quantification was carried out by means of a new and fully validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for new psychoactive substances (NPS) detection. The analysis was performed adding acetonitrile to the samples, the supernatant was dried and reconstituted with methanol. Mephedrone-D3 was used as internal standard. Acquisition was performed through multiple reaction monitoring (MRM) dynamic mode. The MRM transitions used for quantification of 3-MeO-PCP were: m/z 274→86, 121. 3-MeO-PCP was quantified in all the biological samples at the following concentrations: 350.0 (blood) and 6109.2 (urine) ng/mL for A; 180.1 (blood) and 3003.6 (urine) ng/mL for B. Taking into account the analytical results, we can suppose that the manifested symptoms were due to the consumption of 3-MeO-PCP in synergy with alcohol. Our report is the first case of 3-MeO-PCP intoxication in Italy and one of the few documented all over the world. For this reason, this case represents a significant worrisome alarm about the spread of this substance. Here we want to highlight the importance of having an effective and broad-spectrum analytical method in order to face the NPS issue.

Inhaled carbon dioxide causes dose-dependent paradoxical bradypnea in animals anesthetized with pentobarbital, but not with isoflurane or ketamine.

INTRODUCTION: In spontaneously breathing mice anesthetized with pentobarbital, we observed unexpected paradoxical bradypnea following 5% inhaled CO2. METHODS: Observational study 7-8 week CB6F1/OlaHsd mice (n = 99), anesthetized with 30 mg/kg intraperitoneal pentobarbital. Interventional study: Adult male Wistar rats (n = 18), anesthetized either with 30 mg/kg intraperitoneal pentobarbital, 100 mg/kg intraperitoneal ketamine or 1.5% isoflurane. Rats had femoral artery cannulas inserted for hemodynamic monitoring and serial arterial blood gas measurements. RESULTS: Observational study: There was a marked reduction in respiratory rate following 4 min of normoxic hypercapnia; average reduction of 9 breaths/min (p < 0.001) (17% reduction from baseline). Interventional study: increasing CO2 caused dose-dependent increase in respiratory rate for ketamine-xylazine (p = 0.007) and isoflurane (p = 0.016) but dose-dependent decrease in respiratory rate for pentobarbital (p = 0.046). Increasing inspired CO2 caused dose-dependent acidosis following pentobarbital and isoflurane (p = 0.013 and p = 0.017, respectively); but not following ketamine-xylazine (p = 0.58). CONCLUSIONS: Inhaled CO2 caused paradoxical dose-dependent bradypnea in animals anesthetized with pentobarbital, an observation not hitherto reported as a part of anesthesia-related respiratory depression.

Presentation of an experimental method to induce in vitro ("organ chambers") respiratory acidosis and its effect on vascular reactivity.

PURPOSE: To create in vitro a model to generate acidosis by CO2 bubbling "organ chambers", which would be useful for researchers that aim to study the effects of acid-base disturbs on the endothelium-dependent vascular reactivity. METHODS: Eighteen male Wistar rats (230-280 g) were housed, before the experiments, under standard laboratory conditions (12h light/dark cycle at 21°C), with free access to food and water. The protocol for promoting in vitro respiratory acidosis was carried out by bubbling increased concentrations of CO2. The target was to achieve an ideal way to decrease the pH gradually to a value of approximately 6.6.It was used, initially, a gas blender varying concentrations of the carbogenic mixture (95% O2 + 5% CO2) and pure CO2. RESULTS: 1) 100% CO2, pH variation very fast, pH minimum 6.0; 2) 90%CO2 pH variation bit slower, pH minimum 6.31; 3) 70%CO2, pH variation slower, pH minimum 6.32; 4) 50% CO2, pH variation slower, pH minimum 6:42; 5) 40 %CO2, Adequate record, pH minimum 6.61, and; 6) 30 %CO2 could not reach values below pH minimum 7.03. Based on these data the gas mixture (O2 60% + CO2 40%) was adopted. CONCLUSION: This gas mixture (O2 60% + CO2 40%) was effective in inducing respiratory acidosis at a speed that made, possible the recording of isometric force.

Presentation of an experimental method to induce in vitro ("organ chambers") respiratory acidosis and its effect on vascular reactivity

PURPOSE: To create in vitro a model to generate acidosis by CO2 bubbling "organ chambers", which would be useful for researchers that aim to study the effects of acid-base disturbs on the endothelium-dependent vascular reactivity. METHODS: Eighteen male Wistar rats (230-280g) were housed, before the experiments, under standard laboratory conditions (12h light/dark cycle at 21°C), with free access to food and water. The protocol for promoting in vitro respiratory acidosis was carried out by bubbling increased concentrations of CO2. The target was to achieve an ideal way to decrease the pH gradually to a value of approximately 6.6.It was used, initially, a gas blender varying concentrations of the carbogenic mixture (95% O2 + 5% CO2) and pure CO2. RESULTS: 1) 100% CO2, pH variation very fast, pH minimum 6.0; 2) 90%CO2 pH variation bit slower, pH minimum6.31; 3) 70%CO2, pH variation slower, pH minimum 6.32; 4) 50% CO2, pH variation slower, pH minimum 6:42; 5) 40 %CO2, Adequate record, pH minimum 6.61, and; 6) 30 %CO2 could not reach values below pH minimum 7.03. Based on these data the gas mixture (O2 60% + CO2 40%) was adopted, CONCLUSION: This gas mixture (O2 60% + CO2 40%) was effective in inducing respiratory acidosis at a speed that made, possible the recording of isometric force. .

Dynamics of acid-base metabolic compensation and hematological regulation interactions in response to CO2 challenges in embryos of the chicken (Gallus gallus).

CO2 exposure elicits multiple changes in the acid-base balance and hematology of avian embryos, but the time-specific, dose-dependent effects of graded increases in extrinsic CO2 in a normoxic environment are poorly understood. Consequently, we exposed day 15 chicken embryos to 1, 3, 5, 6 or 10% CO2 in 20% O2. We hypothesized that both the magnitude of hypercapnic respiratory acidosis and the resultant metabolic compensation within 24 h of exposure to <10% CO2 are proportional to ambient CO2 concentration ([CO2]). We also predicted that regulation of hematological respiratory variables is graded according to [CO2]. Time-course (2, 6 and 24 h) changes were determined for acid-base disturbances and hematological respiratory variables; hematocrit (Hct), red blood cell concentration ([RBC]), hemoglobin concentration, mean corpuscular volume (MCV) and other mean corpuscular indices. Both the decrease in uncompensated pH, which indicates uncompensated respiratory acidosis, and the compensatory pH increase, a sign of metabolic compensation, increased with [CO2]. The partial metabolic compensation across all CO2 gas mixtures was ~17, 46 and 53% compensation at 2, 6 and 24 h, respectively. Hematological responses were nearly identical across the entire range of [CO2], with Hct decreasing across the time course of CO2 exposure due to a decrease in MCV from 2 to 24 h and a decrease in [RBC] at 24 h. Even though hematological regulation was not graded, chicken embryos were able to compensate and survive exposure to <10% CO2.

A simple and novel method to monitor breathing and heart rate in awake and urethane-anesthetized newborn rodents.

Rodents are most useful models to study physiological and pathophysiological processes in early development, because they are born in a relatively immature state. However, only few techniques are available to monitor non-invasively heart frequency and respiratory rate in neonatal rodents without restraining or hindering access to the animal. Here we describe experimental procedures that allow monitoring of heart frequency by electrocardiography (ECG) and breathing rate with a piezoelectric transducer (PZT) element without hindering access to the animal. These techniques can be easily installed and are used in the present study in unrestrained awake and anesthetized neonatal C57/Bl6 mice and Wistar rats between postnatal day 0 and 7. In line with previous reports from awake rodents we demonstrate that heart rate in rats and mice increases during the first postnatal week. Respiratory frequency did not differ between both species, but heart rate was significantly higher in mice than in rats. Further our data indicate that urethane, an agent that is widely used for anesthesia, induces a hypoventilation in neonates whilst heart rate remains unaffected at a dose of 1 g per kg body weight. Of note, hypoventilation induced by urethane was not detected in rats at postnatal 0/1. To verify the detected hypoventilation we performed blood gas analyses. We detected a respiratory acidosis reflected by a lower pH and elevated level in CO2 tension (pCO2) in both species upon urethane treatment. Furthermore we found that metabolism of urethane is different in P0/1 mice and rats and between P0/1 and P6/7 in both species. Our findings underline the usefulness of monitoring basic cardio-respiratory parameters in neonates during anesthesia. In addition our study gives information on developmental changes in heart and breathing frequency in newborn mice and rats and the effects of urethane in both species during the first postnatal week.

Internet highs--seizures after consumption of synthetic cannabinoids purchased online.

BACKGROUND: Since 2004, a new wave of synthetic cannabinoids (SCs) known as "Spice drugs" has come under scrutiny because of their suspected link to neurological and psychiatric sequelae. These "herbal incense" or "potpourri blends" have gained popularity as a result of being more potent than natural cannabinoids, are not detected with current screening tests, and are easily modified by manufacturers to bypass legal restrictions. Unfortunately, cases of withdrawal phenomena, nausea, hypertension, and psychosis are now being reported in the medical literature. In addition, after reports in lay media of seizures and coma attributed to the consumption of the drug, anecdotal reports have emerged of similar findings in the medical literature. CASE DESCRIPTION: We report on a 48-year-old man who, after consuming the herbal blend, lost consciousness and suffered several episodes of seizures. Despite a complicated ICU stay, the patient recovered well with no subsequent neurological sequelae. CONCLUSIONS: The authors interpreted the history and findings consistent with the consumption of a large amount of synthetic cannabinoids leading to new-onset seizures and coma. However, at the time of admission, the lack of routine laboratory testing and treatment options delayed the diagnosis and delivery of appropriate therapy.

Improved pulmonary vascular reactivity and decreased hypertrophic remodeling during nonhypercapnic acidosis in experimental pulmonary hypertension.

Pulmonary hypertension (PH) is characterized by pulmonary arteriolar remodeling with excessive pulmonary vascular smooth muscle cell (VSMC) proliferation. This results in decreased responsiveness of pulmonary circulation to vasodilator therapies. We have shown that extracellular acidosis inhibits VSMC proliferation and migration in vitro. Here we tested whether induction of nonhypercapnic acidosis in vivo ameliorates PH and the underlying pulmonary vascular remodeling and dysfunction. Adult male Sprague-Dawley rats were exposed to hypoxia (8.5% O(2)) for 2 wk, or injected subcutaneously with monocrotaline (MCT, 60 mg/kg) to develop PH. Acidosis was induced with NH(4)Cl (1.5%) in the drinking water 5 days prior to and during the 2 wk of hypoxic exposure (prevention protocol), or after MCT injection from day 21 to 28 (reversal protocol). Right ventricular systolic pressure (RVSP) and Fulton's index were measured, and pulmonary arteriolar remodeling was analyzed. Pulmonary and mesenteric artery contraction to phenylephrine (Phe) and high KCl, and relaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) were examined ex vivo. Hypoxic and MCT-treated rats demonstrated increased RVSP, Fulton's index, and pulmonary arteriolar thickening. In pulmonary arteries of hypoxic and MCT rats there was reduced contraction to Phe and KCl and reduced vasodilation to ACh and SNP. Acidosis prevented hypoxia-induced PH, reversed MCT-induced PH, and resulted in reduction in all indexes of PH including RVSP, Fulton's index, and pulmonary arteriolar remodeling. Pulmonary artery contraction to Phe and KCl was preserved or improved, and relaxation to ACh and SNP was enhanced in NH(4)Cl-treated PH animals. Acidosis alone did not affect the hemodynamics or pulmonary vascular function. Phe and KCl contraction and ACh and SNP relaxation were not different in mesenteric arteries of all groups. Thus nonhypercapnic acidosis ameliorates experimental PH, attenuates pulmonary arteriolar thickening, and enhances pulmonary vascular responsiveness to vasoconstrictor and vasodilator stimuli. Together with our finding that acidosis decreases VSMC proliferation, the results are consistent with the possibility that nonhypercapnic acidosis promotes differentiation of pulmonary VSMCs to a more contractile phenotype, which may enhance the effectiveness of vasodilator therapies in PH.

Tumor lysis syndrome after sorafenib for hepatocellular carcinoma: a case report.

We encountered a patient who developed marked renal impairment and hyperuricemia in a short period after sorafenib administration, which suggested tumor lysis syndrome (TLS). A 79-year-old woman with hepatitis C-related liver cirrhosis was found to have intermediate hepatocellular carcinoma (HCC) according to Barcelona Clinic Cancer staging classification. Pre-treatment laboratory tests showed mild renal impairment. On the 10th day of sorafenib intake, the creatinine and uric acid levels rose to 2.99 and 16.1 mg/dl, respectively, and arterial blood gas analysis showed respiratory compensated metabolic acidosis, which suggested grade I clinical TLS according to the diagnostic criteria of TLS as defined by Cairo-Bishop. TLS is a group of metabolic abnormalities that arise from the rapid breakdown of many tumor cells upon the initiation of malignant tumor chemotherapy, resulting in the release of intracellular metabolites that exceed the ability of the kidney to excrete them. TLS occurs more rarely in solid tumors, including HCC, than in hematologic malignancies. Sorafenib is administered to patients with renal impairment at recommended doses. However, the drug may cause TLS or severe renal impairment in advanced HCC patients with preexisting mild renal impairment, necessitating reduced-dose therapy and careful follow-up after the start of therapy to facilitate early diagnosis and treatment. This is a very rare complication developed in a short period treated with sorafenib as a single-agent for an advanced HCC.

Mechanisms of respiratory insufficiency induced by methadone overdose in rats.

Methadone may cause respiratory depression. We aimed to understand methadone-related effects on ventilation as well as each opioid-receptor (OR) role. We studied the respiratory effects of intraperitoneal methadone at 1.5, 5, and 15 mg/kg (corresponding to 80% of the lethal dose-50%) in rats using arterial blood gases and plethysmography. OR antagonists, including intravenous 10 mg/kg-naloxonazine at 5 minutes (mu-OR antagonist), subcutaneous 30 mg/kg-naloxonazine at 24 hours (micro1-OR antagonist), 3 mg/kg-naltrindole at 45 minutes (delta-OR antagonist) and 5 mg/kg-Nor-binaltorphimine at 6 hours (kappa-OR antagonist) were pre-administered. Plasma concentrations of methadone enantiomers were measured using high-performance liquid chromatography coupled to mass-spectrometry. Methadone dose-dependent inspiratory time (T(I)) increase tended to be linear. Respiratory depression was observed only at 15 mg/kg and characterized by an increase in expiratory time (T(E)) resulting in hypoxemia and respiratory acidosis. Intravenous naloxonazine completely reversed all methadone-related effects on ventilation, while subcutaneous naloxonazine reduced its effects on pH (P < 0.05), PaCO(2) (P < 0.01) and T(E) (P < 0.001) but only partially on T(I) (P < 0.001). Naltrindole reduced methadone-related effects on T(E) (P < 0.001). Nor-binaltorphimine increased methadone-related effects on pH and PaO(2) (P < 0.05) Respiratory effects as a function of plasma R-methadone concentrations showed a decrease in PaO(2) (EC(50): 1.14 microg/ml) at lower concentrations than those necessary for PaCO(2) increase (EC(50): 3.35 microg/ml). Similarly, increased T(I) (EC(50): 0.501 microg/ml) was obtained at lower concentrations than those for T(E) (EC(50): 4.83 microg/ml). Methadone-induced hypoxemia is caused by mu-ORs and modulated by kappa-ORs. Additionally, methadone-induced increase in T(E) is caused by mu1- and delta-opioid receptors while increase in T(I) is caused by mu-ORs.

Arterial [H+] and the ventilatory response to hypoxia in humans: influence of acetazolamide-induced metabolic acidosis.

In this study, we investigated possible separate effects of H+ ions and CO2 on hypoxic sensitivity in humans. We also examined whether hypoxic sensitivity, conventionally defined as the ratio of (hypoxic - normoxic) ventilation over (hypoxic - normoxic) Hb oxygen saturation can also be estimated by taking the ratio (hypoxic - normoxic) ventilation over (logPa(O2) hypoxia - logPa(O2) normoxia), enabling one to measure the hypoxic response independently from potential confounding influences of changes in position of the Hb oxygen saturation curve. We used acetazolamide to induce a metabolic acidosis. To determine the acute hypoxic response (AHR), we performed step decreases in end-tidal Po2 to approximately 50 Torr lasting 5 min each at three different constant end-tidal Pco2 levels. Nine subjects ingested 250 mg of acetazolamide or placebo every 8 h for 3 days in a randomized double-blind crossover design. The metabolic acidosis was accompanied by a rise in ventilation, a substantial fall in Pa(CO2), and a parallel leftward shift of the ventilatory CO2 response curve. In placebo, CO2 induced equal relative increases in hypoxic sensitivity (O2-CO2 interaction) regardless of the way it was defined. Acetazolamide shifted the response line representing the relationship between hypoxic sensitivity and arterial [H+] ([H+](a)) to higher values of [H+](a) without altering its slope, indicating that it did not affect the O2-CO2 interaction. So, in contrast to an earlier belief, CO2 and H+ have separate effects on hypoxic sensitivity. This was also supported by the finding that infusion of bicarbonate caused a leftward shift of the hypoxic sensitivity-[H+](a) response lines in placebo and acetazolamide. A specific inhibitory effect of acetazolamide on hypoxic sensitivity was not demonstrated.

Normoxic induction of cerebral HIF-1alpha by acetazolamide in rats: role of acidosis.

Acetazolamide has been recognized as an effective treatment for acute mountain sickness. The efficacy of acetazolamide is related to metabolic acidosis, which promotes chemoreceptors to respond to hypoxic stimuli at altitude. In this study, adult male Sprague-Dawley rats were treated with acetazolamide (100mg/kg or 50mg/kg, I.P.) for 3 days. Primary cultured cortical neurons and PC12 cell lines were exposed to acidosis-permissive (pH 6.5) or standard (pH 7.2) media for 20h. HIF-1alpha and its target genes were assayed by Western blot, real-time PCR, HIF-1 DNA-binding assay and chloramphenicol acetyltransferase reporter gene assay. HIF-1alpha protein level and HIF-1 DNA-binding activities were increased in cerebral cortices of rats treated with acetazolamide. Moreover, the mRNA levels of erythropoietin, vascular endothelial growth factor, and glucose transporter-1 also increased. The HIF-1alpha protein level and activity of HIF-driven chloramphenicol acetyltransferase reporters of cortical neurons and PC12 cells treated with acidosis media were significantly enhanced. We conclude that the normoxic induction of HIF-1alpha and HIF-1 mediated genes by acetazolamide may mediate the effect of acetazolamide in the reduction of symptoms of acute mountain sickness.

Acid-base interpretation can be the predictor of outcome among patients with acute organophosphate poisoning before hospitalization.

OBJECTIVES: Acute organophosphate (OP) poisoning causing alteration in acid-base equilibrium was reported before. Hence, different acid-base statuses may present in patients with acute poisoning due to OP exposure. This study aims to determine the impact of acid-base interpretation in patients with acute OP poisoning before hospitalization in medical care units and to describe the pattern of mortality with different acid-base statuses. DESIGN AND PATIENTS: Over a 9-year retrospective study, from July 1996 to August 2005, a total of 82 consecutive patients with acute OP poisoning were admitted to the China Medical University Hospital (Taichung, Taiwan) within 24 hours after exposure to OP and were enrolled into this study. RESULTS: Patients with acute OP poisoning were divided into 4 groups: without acidosis, metabolic acidosis, respiratory acidosis, and mixed acidosis. Overall survival (Kaplan-Meier curves) among groups was statistically significant (P < .0001). The mortality rate of acute OP poisoned patients with metabolic acidosis was 25%, and 75% of those patients died of cardiovascular failure. The mortality rate of acute OP poisoning with respiratory acidosis was 50%, and 50% of those patients died of respiratory failure. CONCLUSIONS: Acid-base interpretation can be effective in quick diagnosis and prediction of the outcome of patients with acute OP poisoning (without acidosis < metabolic acidosis < respiratory acidosis < mixed acidosis) before hospitalization. Major causes of death are different between the respiratory acidosis and metabolic acidosis groups of patients with acute OP poisoning.

Comparison of the effects of caffeine and doxapram on respiratory and cardiovascular function in foals with induced respiratory acidosis.

OBJECTIVE: To determine and compare the effects of caffeine and doxapram on cardiorespiratory variables in foals during isoflurane-induced respiratory acidosis. ANIMALS: 6 clinically normal foals (1 to 3 days old). PROCEDURES: At intervals of > or = 24 hours, foals received each of 3 IV treatments while in a steady state of hypercapnia induced by isoflurane anesthesia (mean +/- SD, 1.4 +/- 0.3% endtidal isoflurane concentration). After assessment of baseline cardiorespiratory variables, a low dose of the treatment was administered and variables were reassessed; a high dose was then administered, and variables were again assessed. Sequential low- and high-dose treatments included doxapram (loading dose of 0.5 mg/kg, followed by a 20-minute infusion at 0.03 mg/kg/min and then 0.08 mg/kg/min), caffeine (5 mg/kg and 10 mg/kg), and saline (0.9% NaCl) solution (equivalent volumes). RESULTS: Administration of doxapram at both infusion rates resulted in a significant increase in respiratory rate, minute ventilation, arterial blood pH, PaO(2), and arterial blood pressure. These variables were also significantly higher during doxapram administration than during caffeine or saline solution administration. There was a significant dose-dependent decrease in PaCO(2) and arterial bicarbonate concentration during doxapram treatment. In contrast, PaCO(2) increased from baseline values after administration of saline solution or caffeine. The PaCO(2) value was significantly lower during doxapram treatment than it was during caffeine or saline solution treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that doxapram restored ventilation in a dose-dependent manner in neonatal foals with isoflurane-induced hypercapnia. The effects of caffeine on respiratory function were indistinguishable from those of saline solution.

Harmful effects and acute lethal toxicity of intravenous administration of low concentrations of hydrofluoric acid in rats.

The acute toxicity of hydrofluoric acid (HFA) was investigated in a 24-h lethal dose study of intravenous infusion in rats. The lethal dose lowest (LDLo) and LD50 were 13.1 and 17.4 mg/kg, respectively. Harmful systemic effects were also studied 1 h after acute sublethal exposure to HFA. The maximum dose was set at 9.6 mg/kg (LD5). Rats were injected with HFA (1.6, 3.2, 6.4 or 9.6 mg/kg), saline, sodium fluoride (NaF) or HCl solution. NaF and HCl solution concentrations corresponded to the F- and H+ concentrations of 9.6 mg/kg HFA. Blood urea nitrogen (BUN) and Cr were significantly increased in response to HFA concentrations greater than 3.2mg/kg. Acute glomerular dysfunction also occurred at HFA concentrations greater than 3.2 mg/kg. HCO3- and base excess (BE) were significantly decreased in the 6.4 and 9.6 mg/kg groups. Ca2+ was significantly decreased, and K+ was increased in the 9.6 mg/kg group. BUN was significantly increased in the NaF and HFA groups and was increased in the HFA group compared with that in the NaF group. Cr was significantly increased in the HFA group only. HCO3- and BE were significantly decreased in the NaF and HFA groups and were increased in the HFA group compared with values in the NaF group. Ca2+ was significantly decreased in the NaF and HFA groups, and K+ was significantly increased in the NaF and HFA groups. F- exposure directly affected serum electrolytes. Mortality was thought to be due to cardiac arrhythmia resulting from hypocalcemia and hyperkalemia. Metabolic acidosis and renal failure were more severe in response to HFA exposure than in response to NaF exposure because of more free F-, which has strong cytotoxicity, in the HFA group than in the NaF group. Lethal effects of HFA are promoted by exposure routes such as inhalation that cause rapid absorption into the body. Even low exposure to HFA can cause acute renal dysfunction, electrolyte abnormalities and metabolic acidosis. These complications result in a poor prognosis.