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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 PCO 2 , resulting in decreased arterial pH and PO 2 , as well as increased PCO 2 . 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, PCO 2 , PaO 2 and SaO 2 were studied by plotting time series graphs. Significant changes were defined as pH <7.30, SaO 2  < 90, and PCO 2  > 50 mmHg., Results: No significant change in pH, PCO 2 , PaO 2 and SaO 2 was noted in 4/18 (22%) subjects. A significant drop in SaO 2 was noted in 4/18 (22%). A significant change in PCO 2 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 SaO 2 , but developed respiratory acidosis. At the end of the case, 5/18 (28%) subjects had respiratory acidosis with normal PaO 2 ., 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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2015 Elsevier B.V. All rights reserved.)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

1-Propanol and 2-propanol are isomers of an alcohol with three carbons. They are colorless liquids with a sweet odor. 1-Propanol is metabolized by alcohol dehydrogenase to propionic acid and presents with metabolic acidosis and elevated anion gap, whereas 2-propanol is metabolized by alcohol dehydrogenase to acetone and presents with rapidly developing (within 3-4 h after exposure) ketosis and ketonuria but without metabolic acidosis. We report a patient who simultaneously ingested a lethal dose of 1-propanol and 2-propanol as a hand disinfectant in hospital. The patient lost consciousness and stopped breathing within half an hour after ingestion. He was intubated and artificially ventilated. Initial laboratory results showed mixed acidosis with elevated anion gap, but ketonuria appeared only 12 h after admission and 6 h following the regaining of consciousness. Therefore, laboratory results in simultaneous poisoning with two isomers of alcohol are not just a sum of laboratory results obtained in isolated poisoning with each isomer because they influence each other's metabolism: 1-propanol retards the metabolism of 2-propanol to acetone. In conclusion, 1-propanol and 2-propanol poisoning presents early with mixed acidosis and elevated anion gap and only later with ketonuria.

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.

An Asian multiparous woman weighing 47 kg, who suffered from a rare myopathy, congenital fibre type disproportion, was given morphine 10 mg intramuscularly for labour analgesia. After delivery, she had diastolic hypertension and proteinuria and was prescribed magnesium sulphate. Some hours later she became unresponsive with little respiratory effort. Blood gas analysis revealed a respiratory acidosis. Naloxone administration reversed the symptoms. Further doses were required as the respiratory depression recurred. Opioid-related narcosis is the most likely diagnosis in this case. Other possible differential diagnoses were magnesium overdose or a post-ictal state. The presence of a myopathy could render this patient susceptible to the respiratory effects of opioids. Other explanations for an exaggerated and delayed response to opioids include co-administration of other respiratory depressant drugs such as magnesium sulphate, co-morbidity such as renal impairment and genetic variability in the metabolism of morphine. Robust guidelines and highlighting patients with risk factors are required to prevent this complication from recurring.

Cerebral hypoxia has been proposed as a mechanism by which prenatal ethanol exposure causes fetal alcohol spectrum disorder (FASD) in children, but no study had tested this hypothesis using a chronic exposure model that mimicks a common human exposure pattern. Pregnant sheep were exposed to ethanol, 0.75 or 1.75 g kg(-1) (to create blood ethanol concentrations of 85 and 185 mg dl(-1), respectively), or saline 3 days per week in succession (a 'binge drinking' model) from gestational day (GD) 109 until GD 132. Fetuses were instrumented on GD 119-120 and studied on GD 132. The 1.75 g kg(-1) dose resulted in a significant increase in fetal biventricular output (measured by radiolabelled microsphere technique) and heart rate, and a reduction of mean arterial pressure and total peripheral resistance at 1 h, the end of ethanol infusion. The arterial partial pressure of CO(2) was increased, arterial pH was decreased and arterial partial pressure of O(2) did not change. Fetal whole-brain blood flow increased by 37% compared with the control group at 1 h, resulting in increased cerebral oxygen delivery. The elevation in brain blood flow was region specific, occurring preferentially in the ethanol-sensitive cerebellum, increasing by 44% compared with the control group at 1 h. There were no changes in the lower dose group. Assessment of regional differences in the teratogenic effects of ethanol by stereological cell-counting technique showed a reduced number of cerebellar Purkinje cells in response to the 1.75 g kg(-1) dose compared with the control brains. However, no such differences in neuronal numbers were observed in the hippocampus or the olfactory bulb. We conclude that repeated exposure to moderate doses of ethanol during the third trimester alters fetal cerebral vascular function and increases blood flow in brain regions that are vulnerable to ethanol in the presence of acidaemia and hypercapnia, and in the absence of hypoxia.

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.

Background: Dexamethasone (Dex) limits and all-trans-retinoic acid (RA) promotes alveolarization. While structural changes resulting from such hormonal exposures are known, their functional consequences are unclear., Methods: Neonatal rats were treated with Dex and/or RA during the first two weeks of life or were given RA after previous exposure to Dex. Morphology was assessed by light microscopy and radial alveolar counts. Function was evaluated by plethysmography at d13, pressure volume curves at d30, and exercise swim testing and arterial blood gases at both d15 and d30., Results: Dex-treated animals had simplified lung architecture without secondary septation. Animals given RA alone had smaller, more numerous alveoli. Concomitant treatment with Dex + RA prevented the Dex-induced changes in septation. While the results of exposure to Dex + RA were sustained, the effects of RA alone were reversed two weeks after treatment was stopped. At d13, Dex-treated animals had increased lung volume, respiratory rate, tidal volume, and minute ventilation. On d15, both RA- and Dex-treated animals had hypercarbia and low arterial pH. By d30, the RA-treated animals resolved this respiratory acidosis, but Dex-treated animals continued to demonstrate blood gas and lung volume abnormalities. Concomitant RA treatment improved respiratory acidosis, but failed to normalize Dex-induced changes in pulmonary function and lung volumes. No differences in exercise tolerance were noted at either d15 or d30. RA treatment after the period of alveolarization also corrected the effects of earlier Dex exposure, but the structural changes due to RA alone were again lost two weeks after treatment., Conclusion: We conclude that both RA- and corticosteroid-treatments are associated with respiratory acidosis at d15. While RA alone-induced changes in structure andrespiratory function are reversed, Dex-treated animals continue to demonstrate increased respiratory rate, minute ventilation, tidal and total lung volumes at d30. Concomitant treatment with Dex + RA prevents decreased septation induced by Dex alone and results in correction of hypercarbia. However, these animals continue to have abnormal pulmonary function and lung volumes. Increased septation as a result of RA treatment alone is reversed upon discontinuation of treatment. These data suggest that Dex + RA treatment results in improved gas exchange likely secondary to normalized septation.

To investigate whether hypercapnic acidosis, induced by adding CO2 to inspired gas, would be protective effect against ventilator-induced lung injury (VILI), we ventilated 55 normal white rabbits for 6 hr or until PaO2/FIO2 <200 mmHg. Control group (n=15) was ventilated with peak inspiratory pressure (PIP) of 15 cm H2O, positive end-expiratory pressure (PEEP) of 3 cm H2O, an inspiration-to-expiration ratio of 1:2, and an inspired oxygen fraction (FIO2) of 0.40. High pressure hypercapnic group (HPHC; n=20) was ventilated with PIP of 30 cm H2O, PEEP of 0 cm H2O, and FIO2 of 0.40. Carbon dioxide was introduced into the inspiratory limb of the ventilator circuit, as necessary to maintain hypercapnia (PaCO2, 65 to 75 mmHg). High pressure normocapnic group (HPNC; n=20) was ventilated with same setting of HPHC, except normocapnia (PaCO2, 35 to 45 mmHg). Bronchoalveolar lavage fluid (BALF) lactate dehydrogenase, aspartate aminotransferase, interleukin-8 were significantly higher in high pressure ventilator group than control group (p<0.05). Wet weight to dry weight (WW/DW) and histologic scores were significantly higher in high pressure ventilator group than control group (p<0.05). However, there were no significant differences in oxygenation, BALF inflammatory markers, WW/DW and histologic scores between HPHC and HPNC groups. These findings suggest that hypercapnic acidosis at least induced by CO2 insufflation would not be protective effect against VILI in this model.

Previous reports suggest that an important characteristic of chemosensitive neurones is an unusually large change of steady-state intracellular pH in response to a change in extracellular pH (DeltapH(i)/DeltapH(o)). To determine whether such a correlation exists between neurones from the medullary raphe (a chemosensitive brain region) and hippocampus (a non-chemosensitive region), we used BCECF to monitor pH(i) in cultured neurones subjected to extracellular acid-base disturbances. In medullary raphe neurones, respiratory acidosis (5%--> 9% CO(2)) caused a rapid fall in pH(i) (DeltapH(i) approximately 0.2) with no recovery and a large DeltapH(i)/DeltapH(o) of 0.71. Hippocampal neurones had a similar response, but with a slightly lower DeltapH(i)/DeltapH(o) (0.59). We further investigated a possible link between pH(i) regulation and chemosensitivity by following the pH(i) measurements on medullary raphe neurones with an immunocytochemistry for tryptophan hydroxylase (a marker of serotonergic neurones). We found that the DeltapH(i)/DeltapH(o) of 0.69 for serotonergic neurones (which are stimulated by acidosis) was not different from either the DeltapH(i)/DeltapH(o) of 0.75 for non-serotonergic neurones (most of which are not chemosensitive), or from the DeltapH(i)/DeltapH(o) of hippocampal neurones. For both respiratory alkalosis (5%--> 3% CO(2)) and metabolic alkalosis (22 mm--> 35 mm HCO(3)(-)), DeltapH(i)/DeltapH(o) was 0.42-0.53 for all groups of neurones studied. The only notable difference between medullary raphe and hippocampal neurones was in response to metabolic acidosis (22 mm--> 14 mm HCO(3)(-)), which caused a large pH(i) decrease in approximately 80% of medullary raphe neurones (DeltapH(i)/DeltapH(o)= 0.71), but relatively little pH(i) decrease in 70% of the hippocampal neurones (DeltapH(i)/DeltapH(o)= 0.09). Our comparison of medullary raphe and hippocampal neurones indicates that, except in response to metabolic acidosis, the neurones from the chemosensitive region do not have a uniquely high DeltapH(i)/DeltapH(o). Moreover, regardless of whether neurones were cultured from the chemosensitive or the non-chemosensitive region, pH(i) did not recover during any of the acid-base stresses.

Clinical reports on unintentional mass exposure to extreme concentrations of carbon dioxide are rare. We describe an industrial incident caused by a container of liquid carbon dioxide that was unintentionally opened in an enclosed working environment. Twenty-five casualties reached our emergency department. Symptoms included dyspnea, cough, dizziness, chest pain, and headache. ECGs (n=15) revealed ST-segment changes in 2 (13.3%) patients, atrial fibrillation in 2 patients, and non-Q wave myocardial infarction in 1 patient. Chest radiographs (n=22) revealed diffuse or patchy alveolar patterns, consistent with pneumonitis, in 6 (27%) patients and pulmonary edema in 2 (9%) patients. Eleven (44%) patients were admitted to the hospital: 8 were discharged 24 hours later and the others within 8 days. No patient died. Exposure to high concentrations of carbon dioxide resulted in significant but transient cardiopulmonary morbidity with no mortality when victims were promptly evacuated and given supportive therapy. Cardiac complications were frequently observed and should be actively sought.

High concentration carbon dioxide (CO(2)) is used to promote pre-slaughter anaesthesia in swine and poultry, as well as short-lasting surgical anaesthesia and euthanasia in laboratory animals. Questions related to animal welfare have been raised, as CO(2) anaesthesia does not set in momentarily. Carbon dioxide promotes anaesthesia by lowering the intracellular pH in the brain cells, but the dynamics of the changes in response to a high concentration of CO(2) is not known. Based on (31)P NMR spectroscopy, we describe CO(2)-induced changes in intracellular pH in the brains of five pigs inhaling 90% CO(2) in ambient air for a period of 60 s, and compare the results to changes in arterial blood pH, P(CO2), O(2) saturation and HCO(3)(-) concentration. The intracellular pH paralleled the arterial pH and P(CO2) during inhalation of CO(2); and it is suggested that the acute reaction to CO(2) inhalation mainly reflects respiratory acidosis, and not metabolic regulation as for example transmembrane fluxes of H(+)/HCO(3)(-). The intracellular pH decreased to approximately 6.7 within the 60 s inhalation period, and the situation was metabolically reversible after the end of CO(2) inhalation. The fast decrease in intracellular pH supports the conclusion that high concentration CO(2) leads to anaesthesia soon after the start of inhalation.

We compared the hemodynamic and respiratory effects, recovery time, and cost of two gas inhalants (isoflurane and sevoflurane) for anesthetic induction and maintenance of beaver (Castor canadensis) during surgery to implant radio transmitters in the peritoneal cavity. Heart rate, respiratory rate, relative hemoglobin saturation with oxygen (SpO2), and body temperature were measured every 5 min for the first 45 min, and arterial blood gas was measured once, 25 min into the anesthetic procedure. Induction for either agent was smooth and rapid. Heart rate and respiratory rate both decreased during the procedure though neither was lower than baseline values reported in the literature for beaver. Relative hemoglobin saturation with oxygen, body temperature, and blood gas variables did not differ between each anesthetic regime. Both inhalants caused slight respiratory acidosis. Recovery time from anesthesia was highly variable (1-178 min) but did not differ statistically between drugs. Sevoflurane costs ($22.30/60 min) were much higher than isoflurane costs ($3.50/60 min). We recommend isoflurane or sevoflurane for anesthetic induction and maintenance of beaver because of the lack of physiologic differences.

Unlabelled: In this study, we compared the effects of large intravascular volume infusion of 0.9% saline (NS) or lactated Ringer's (LR) solution on electrolytes and acid base balance during major spine surgery and evaluated the postoperative effects. Thirty patients aged 18-70 yr were included in the study. General anesthesia was induced with 5 mg/kg thiopental and 0.1 mg/kg vecuronium IV. Anesthesia was maintained with oxygen in 70% nitrous oxide and 1.5%-2% sevoflurane. In Group I, the NS solution, and in Group II, the LR solution were infused 20 mL. kg(-1). h(-1) during the operation and 2.5 mL. kg(-1). h(-1), postoperatively. Electrolytes (Na+, K+, Cl-) and arterial blood gases were measured preoperatively, every hour intraoperatively and at the 1st, 2nd, 4th, 6th, and 12th hours postoperatively. In the NS group, pHa, HCO3 and base excess decreased, and Cl- values increased significantly at the 2nd hour and Na+ values increased at the 4th hour intraoperatively (P < 0.001). The values returned to normal ranges at the 12th hour postoperatively. In the LR group, blood gas analysis and electrolyte values did not show any significant difference intraoperatively, but the increase in PaCO2 and the decrease in pHa and serum Na+ was significant at the 1st hour postoperatively. Although intraoperative 20 mL. kg(-1). h(-1) LR infusion does not cause hyperchloremic metabolic acidosis as does NS infusion, it leads to postoperative respiratory acidosis and mild hyponatremia., Implications: The infusion of large-volume lactated Ringer's solution does not cause hyperchloremic metabolic acidosis as does 0.9% saline during major surgery, but leads to postoperative mild hyponatremia and respiratory acidosis.

This report describes a patient with mixed normal anion gap hyperchloremic metabolic and respiratory acidosis associated with hypokalemia attributed to cough mixture abuse. Metabolic acidosis was likely related to an overdose of ammonium chloride, whereas respiratory acidosis was probably related to the effect of hypokalemia on respiratory muscles, causing hypoventilation. Hypokalemia was caused by a transcellular shift of potassium induced by ephedrine and pseudoephedrine. Both ammonium chloride and ephedrine were probably present in the cough mixture obtained by our patient as an over-the-counter medication. Physicians should be aware of the potential for cough mixture abuse to cause major electrolyte disturbances that may carry the risk for major cardiac arrhythmias, particularly in youth.

Fumonisin B(1) is the most toxic and commonly occurring form of a group of mycotoxins that alter sphingolipid biosynthesis and induce leukoencephalomalacia in horses and pulmonary edema in pigs. Purified fumonisin B(1) (1 mg/kg, iv, daily) increased serum sphinganine and sphingosine concentrations and decreased cardiovascular function in pigs within 5 days. We therefore examined whether the same dosage schedule of fumonisin B(1) produced a similar effect in calves. Ten milk-fed male Holstein calves were instrumented to obtain blood and cardiovascular measurements. Treated calves (n = 5) were administered purified fumonisin B(1) at 1 mg/kg, iv, daily for 7 days and controls (n = 5) were administered 10 ml 0.9% NaCl, iv, daily. Each calf was euthanized on day 7. In treated calves, serum sphinganine concentration increased from day 3 onward (day 7, 0.237 +/- 0.388 micromol/l; baseline, 0.010 +/- 0.007 micromol/l; mean +/- SD), whereas, serum sphingosine concentration was unchanged (day 7, 0.044 +/- 0.065 micromol/l; baseline, 0.021 +/- 0.025 micromol/l). Heart rate, cardiac output, stroke volume, mean arterial pressure, mean pulmonary artery pressure, pulmonary artery wedge pressure, central venous pressure, plasma volume, base-apex electrocardiogram, arterial Po(2), and systemic oxygen delivery were unchanged in treated and control calves. Fumonisin-treated calves developed metabolic acidosis (arterial blood pH, 7.27 +/- 0.11; base excess, -9.1 +/- 7.6 mEq/l), but all survived for 7 days. We conclude that calves are more resistant to fumonisin B(1) cardiovascular toxicity than pigs.

Background: Previous research suggested that splanchnic hypoperfusion occurs after resuscitation with certain acellular hemoglobin solutions. We examined the influence of maltose content and oxygen affinity on resuscitation with various hemoglobin polyoxyethylene conjugate solutions after hemorrhage., Methods: Fifteen swine underwent hemorrhage and equal volume resuscitation with pyridoxalated hemoglobin polyoxyethylene conjugate containing 0% or 8% maltose, or low P50 conjugate, which also contained 8% maltose. Five control animals were monitored but not bled. Regional blood flow was determined by using radioactive microspheres, gastric mucosal perfusion was estimated with tonometry, and gut histopathology was evaluated., Results: All hemoglobin solutions produced vasoconstriction, manifested by elevated mean systemic and pulmonary artery pressures without a significant decrease in cardiac index compared with the sham group. Resuscitation with maltose-containing solutions elevated arterial and regional PCO2 and depressed arterial pH and gastric pHi (p < 0.05 for all). Splanchnic and renal blood flows were reduced in the low P50 + 8% maltose group (p < 0.05 vs. sham and baseline for renal blood flow), possibly indicating greater regional vasoconstriction in this group. Ileal mucosal damage was more severe in the maltose-containing groups and correlated with decreased pHi., Conclusion: Vasoconstriction occurred in all groups but was more severe in the low P50 + 8% maltose group. Maltose-containing solutions caused respiratory acidosis, decreased pHi, and histologic evidence of mucosal injury. Pyridoxalated hemoglobin polyoxyethylene conjugate without maltose was a superior resuscitation solution in this swine model.

The influence of carbon dioxide (CO2) on cochlear blood flow (CBF), blood pressure (SBP) and skin blood flow (SBF) was studied in anaesthetized guinea pigs. A transient acute respiratory acidosis was produced by inhalation of CO2 and oxygen (O2) gas mixtures. The blood flows were measured by laser Doppler flowmetry (LDF). High CO2 increased CBF and SBP, and decreased SBF in a dose-dependent manner. The responses of CBF, SBP and SBF to high CO2 were reversible. Our results indicate that high CO2 (and low pH) dilates the smooth muscle of the blood vessels, resulting in an increase in CBF. CO2 also activates the sympathetic nervous system in the whole body, producing an increase in SBP. The distribution of alpha-adrenergic fibres receptors is abundant in skin and scarce in the cochlea. The constrictive effect on blood vessels is much greater in the skin than in the cochlea, thus our results showed a decrease in SBF during stimulation with higher CO2.

To study the possible benefits of N2O pneumoperitoneum, 40 patients scheduled for laparoscopic cholecystectomy for symptomatic cholelithiasis were randomized into either CO2-induced (n = 20) or N2O-induced (n = 20) pneumoperitoneum groups. The intensity of postoperative pain was assessed by the patients themselves using an visual analogue pain score scale. CO2 insufflation caused respiratory acidosis. The total amount of anesthetic enflurane needed was lower in the N2O than in the CO2 group (p < 0.041). The N2O group experienced less pain 1 hour (p < 0.040) and 6 hours (p < 0.017) postoperatively and the next morning. Serum cortisol and plasma adrenaline concentrations in the N2O group did not differ from those in the CO2 group. Patients with N2O pneumoperitoneum seem to have less pain without the side effects caused by CO2. The N2O pneumoperitoneum is a good alternative to the CO2 pneumoperitoneum, especially for prolonged laparoscopic operations in patients with chronic cardiopulmonary diseases.

Background: Chronic respiratory acidosis induced by an elevated carbon dioxide (CO2) environment should provoke hypercalciuria with related total body and subsequent bone calcium losses. We examined this hypothesis in four healthy male volunteers, who were exposed during a 25-d period to an 0.7% CO2 environment within a deep diving isolation chamber. Three months later the same subjects were reexamined during a second campaign being exposed to a 1.2% CO2 atmosphere., Methods: The subjects received a constant calcium intake (1.4 g.d-1) and vitamin D supplement (1000 IU.d-1) during both campaigns. Calcium balance (oral calcium intake minus urinary and fecal calcium output) was evaluated. Serum calcium concentrations and biomarkers of bone metabolism were measured, in order to evaluate bone turnover. Additionally, the response to an acute oral calcium load was examined as a sensitive measure of changes in calcium metabolism., Results: Both, urinary calcium excretion (from 245 +/- 38 to 199 +/- 31 mg.d-1; mean +/- SE, 0.7% and 1.2%, respectively) and fecal calcium losses (from 1229 +/- 128 to 996 +/- 62 mg.d-1) were significantly reduced in the higher (1.2%) CO2 atmosphere. Although more calcium was retained in the body during the 1.2% than during the 0.7% CO2 campaign, serum calcium concentrations and biomarkers of bone formation were significantly lower in the higher CO2 campaign. Furthermore, bone resorption was slightly increased in the 1.2% experiment., Conclusion: Elevated CO2 atmosphere may dose-dependently preserve body calcium without a parallel improvement of bone substance.

Carbon dioxide is the most commonly used gas for abdominal insufflation in laparoscopy today. Due to the solubility of carbon dioxide large volumes are absorbed into the circulation causing a high PCO2 and a low pH (respiratory acidosis). Carbon dioxide is also stored in several sites in the body and is released at the conclusion of the procedure prolonging the respiratory acidosis when the patient is least able to cope with this additional burden. Cardiac effects of CO2 consist of a lowering of the arrhythmia threshold, increased blood pressure, pulse and cardiac output. At a sustained high level this can lead to cardiac depression and death. These effects are particularly prone to occur in cardiac and respiratory cripples. Other gases that have been used include air, oxygen, nitrous oxide and nitrogen. Their use has been discontinued because of the danger of embolism. Air, oxygen and nitrous oxide are also not safe to use in the presence of electrosurgical instruments thereby limiting their usefulness even further. Helium has been proposed as a very promising alternative to CO2. In the laboratory and in a clinical trial, helium has not produced the respiratory acidosis associated with CO2 insufflation. This is further evidence that the acidosis is not primarily due to elevation of the diaphragm and consequent increased dead space, but to the large amount of CO2 that is absorbed directly from the peritoneal cavity. Helium would seem to be the gas of choice at this time as it comes close to fitting the criteria for an ideal insufflating gas. Helium is clear and colorless, allowing unimpeded vision to the operator. It is non toxic, not flammable or explosive and can be safely used with electrocautery and laser. Helium is easy to handle and not very soluble which decreases the amount absorbed from the peritoneal cavity and consequently the amount used. That which is absorbed is quickly cleared by the lungs. Helium is metabolically inactive (in contrast to CO2) and does not interfere with normal metabolic processes. In view of this promising initial work, further studies are indicated.

Laparoscopy has become a routine part of many major and minor surgical procedures. During laparoscopic procedures, carbon dioxide (CO2) is insufflated into the peritoneal cavity to allow visualization of the abdominal viscera. Delay in the elimination of CO2 during the intraoperative and postoperative phases of a laparoscopic procedure has recently been identified. This case study discusses a patient with CO2 toxicity related to the insufflation of CO2 during a laparoscopic procedure. Nurses in the PACU must be alert to the signs of CO2 toxicity after a laparoscopic procedure and be able to correctly interpret arterial blood gases.

Metabolic acidosis can be caused by a variety of pathological conditions, but intoxication with ethylene glycol or methanol should be suspected in cases of a combined increase of osmolal and anion gaps. The determination of the gaps is based on readily available laboratory tests, and the results is known soon after the blood sample is taken. This procedure is of particular interest for hospitals where specific analyses for methanol and ethylene glycol are not available, since calculation of the gap can give an early indication of what treatment to use. Therefore, the gaps should be calculated as a routine in patients with metabolic acidosis of unknown origin. The authors describe the principles for calculating and using the gaps, and report three cases which illustrate their usefulness in practice.

Intracellular calcium toxicity appears to play a major role in cell death during cerebral ischemia. Such calcium enters the cell mainly through the N-methyl-D-aspartate subclass of the postsynaptic glutamate receptor. Increased extracellular hydrogen ion concentration has been shown recently to reduce N-methyl-D-aspartate-activated divalent cation currents. Therefore, we studied the effect of induced brain acidosis, via hypercarbic ventilation, as a potential therapeutic modality in focal cerebral ischemia. Brain acidosis reduced infarct volume in a biphasic manner, with maximal protection at approximately brain pH 6.8. The effect was lost at pH 6.5, presumably due to the effect of acidosis on glial glutamate uptake.

The present study was conducted to examine the roles of hormonal factors in plasma potassium alterations in acute respiratory acidosis. Respiratory acidosis (pH, 7.07-7.10) induced by the inhalation of 10% CO2, 20% O2 and 70% N2 mixed gas caused an increase in the plasma potassium concentration beyond that of the control of 3.44 +/- 0.12 (mean +/- SE) to 4.36 +/- 0.07 mEq/l (p less than 0.01) within 180 min. The plasma norepinephrine concentration was also noted to significantly increase at the same time. Phentolamine (40 micrograms/kg/min i.v.) did not affect the degree of acidosis or acidosis-induced hyperkalemia. No significant changes in the plasma levels of epinephrine, insulin, glucagon, cortisol or aldosterone could be detected. Hormonal factors would thus appear not to be essential to potassium movement from intracellular to extracellular compartments in acute respiratory acidosis.

This prospective study evaluates the extent and temporal course of the cardiorespiratory effects of CO2 during laparoscopic cholecystectomy in otherwise healthy patients. Sixteen patients (M:F = 3:13, average age = 40.2 +/- 14.1 years) were monitored with capnography, transesophageal cardiac output, continuous blood pressure, heart rate, and pulse oximetry. Arterial blood gases were obtained immediately before insufflation of the abdomen with CO2 and before desufflation. Average operative time was 137 +/- 13 minutes. Patients were paralyzed and mechanically ventilated. Minute ventilation was increased if EtCO2 exceeded 45 mmHg or rose by more than 12 mmHg from baseline. End tidal (EtCO2) and arterial CO2 (PaCO2) increased from 31.4 +/- 0.7 mmHg to 42.1 +/- 1.6 mmHg and 33.3 +/- 0.7 mmHg to 43.7 +/- 1.2 mmHg, respectively, during the course of the procedure. Arterial pH decreased from 7.43 +/- 0.01 to 7.34 +/- 0.01, while bicarbonate concentration remained unchanged. Thirteen of the 16 patients required increased minute ventilation due to hypercarbia detected by capnography. Blood pressure increased from 78 +/- 2 mmHg (mean) at the start to 98 +/- 2 mmHg. This increase was coincidental with the maximal PaCO2. Good agreement was observed between paired EtCO2 and PaCO2 measurements. Laparoscopic cholecystectomy with carbon dioxide insufflation causes significant respiratory acidosis and associated cardiovascular changes in otherwise healthy patients. Careful monitoring and cautious application of this technique in patients with pre-existing cardiopulmonary disorders will be required to prevent acute decompensation.

Terbutaline is a beta-sympathomimetic agent that has gained wide use in obstetrics as a tocolytic agent. In addition to inhibiting uterine contractions, terbutaline can cause other clinically significant beta-mediated effects. Terbutaline readily crosses the placenta, and both fetal and neonatal toxicity have been reported. We report possible cardiovascular toxicity secondary to long-term prenatal terbutaline exposure involving three preterm infants of a quadruplet pregnancy. The infants developed cardiovascular decompensation with bradycardia, metabolic acidosis, poor tissue perfusion, and decreased urine output. The infants' conditions were resistant to all routine interventions but responded well to dobutamine infusion. We theorize that long-term prenatal beta-mimetic exposure led to downregulation of fetal beta-receptors. This resulted in impaired myocardial function, increased peripheral vascular resistance, and poor cardiac output. We suggest that neonates with a history of prenatal exposure to terbutaline should be observed closely after birth for any evidence of cardiovascular deterioration.

We report two cases of aluminium phosphide poisoning who presented with rare manifestations, one with bleeding diathesis, hepatitis and acute tubular necrosis and the other with acute respiratory failure.