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Administering sodium bicarbonate (NaHCO 3 ) to patients with respiratory acidosis breathing spontaneously is contraindicated because it increases carbon dioxide load and depresses pulmonary ventilation. Nonetheless, several studies have reported salutary effects of NaHCO 3 in patients with respiratory acidosis but the underlying mechanism remains uncertain. Considering that such reports have been ignored, we examined the ventilatory response of unanesthetized dogs with respiratory acidosis to hypertonic NaHCO 3 infusion (1 N, 5 mmol/kg) and compared it with that of animals with normal acid-base status or one of the remaining acid-base disorders. Ventilatory response to NaHCO 3 infusion was evaluated by examining the ensuing change in PaCO 2 and the linear regression of the PaCO 2 vs. pH relationship. Strikingly, PaCO 2 failed to increase and the ΔPaCO 2 vs. ΔpH slope was negative in respiratory acidosis, whereas PaCO 2 increased consistently and the ΔPaCO 2 vs. ΔpH slope was positive in the remaining study groups. These results cannot be explained by differences in buffering-induced decomposition of infused bicarbonate or baseline levels of blood pH, PaCO 2 , and pulmonary ventilation. We propose that NaHCO 3 infusion improved the ventilatory efficiency of animals with respiratory acidosis, i.e., it decreased their ratio of total pulmonary ventilation to carbon dioxide excretion (V E /V CO2 ). Such exclusive effect of NaHCO 3 infusion in animals with respiratory acidosis might emanate from baseline increased V D /V T (dead space/tidal volume) caused by bronchoconstriction and likely reduced pulmonary blood flow, defects that are reversed by alkali infusion. Our observations might explain the beneficial effects of NaHCO 3 reported in patients with acute respiratory acidosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Botulinum neurotoxin (BoNT) is a potent protein toxin that causes muscle paralysis and death by asphyxiation. Treatments for symptomatic botulism are intubation and supportive care until respiratory function recovers. Aminopyridines have recently emerged as potential treatments for botulism. The clinically approved drug 3,4-diaminopyridine (3,4-DAP) rapidly reverses toxic signs of botulism and has antidotal effects when continuously administered in rodent models of lethal botulism. Although the therapeutic effects of 3,4-DAP likely result from the reversal of diaphragm paralysis, the corresponding effects on respiratory physiology are not understood. Here, we combined unrestrained whole-body plethysmography (UWBP) with arterial blood gas measurements to study the effects of 3,4-DAP, and other aminopyridines, on ventilation and respiration at terminal stages of botulism in mice. Treatment with clinically relevant doses of 3,4-DAP restored ventilation in a dose-dependent manner, producing significant improvements in ventilatory parameters within 10 minutes. Concomitant with improved ventilation, 3,4-DAP treatment reversed botulism-induced respiratory acidosis, restoring blood levels of CO 2 , pH, and lactate to normal physiologic levels. Having established that 3,4-DAP-mediated improvements in ventilation were directly correlated with improved respiration, we used UWBP to quantitatively evaluate nine additional aminopyridines in BoNT/A-intoxicated mice. Multiple aminopyridines were identified with comparable or enhanced therapeutic efficacies compared with 3,4-DAP, including aminopyridines that selectively improved tidal volume versus respiratory rate and vice versa. In addition to contributing to a growing body of evidence supporting the use of aminopyridines to treat clinical botulism, these data lay the groundwork for the development of aminopyridine derivatives with improved pharmacological properties. SIGNIFICANCE STATEMENT: There is a critical need for fast-acting treatments to reverse respiratory paralysis in patients with botulism. This study used unrestrained, whole-body plethysmography and arterial blood gas analysis to show that aminopyridines rapidly restore ventilation and respiration and reverse respiratory acidosis when administered to mice at terminal stages of botulism. In addition to supporting the use of aminopyridines as first-line treatments for botulism symptoms, these data are expected to contribute to the development of new aminopyridine derivatives with improved pharmacological properties., (Copyright © 2024 by The Author(s).)

Objective: Acidosis decreases myocardial contractile and myofibrillar responsiveness by reducing the calcium sensitivity of contractile proteins, which could reduce the effectiveness of pimobendan. We aimed to assess the cardiovascular effects of pimobendan in dogs subjected to acute respiratory acidosis., Design: Randomized crossover study with a 2-week washout period., Setting: University Laboratory., Animals: Six healthy research Beagle dogs., Interventions: Anesthetized dogs were administered 2 doses of IV pimobendan during conditions of eucapnia (Paco 2 35-40 mm Hg) and hypercapnia (Paco 2 90-110 mm Hg). Eucapnia was maintained by positive pressure ventilation and hypercapnia was induced by adding exogenous CO 2 to the anesthesia circuit. Heart rate (HR), systemic arterial blood pressure, cardiac output (CO), systemic and pulmonary vascular resistance (SVR and PVR, respectively), and pulmonary arterial pressure (PAP) were measured at baseline and 60 min after administering 0.125 mg/kg (low) and 0.25 mg/kg (high) pimobendan intravenously. Blood gas and biochemical analyses were performed at baseline and at the end of the experiment., Measurements and Main Results: The median baseline blood pH was 7.41 (range: 7.33-7.45) and 7.03 (range: 6.98-7.09) under conditions of eucapnia and hypercapnia, respectively. The serum concentrations of epinephrine and norepinephrine and the HR, CO, and PAP were higher, and SVR was lower at baseline in hypercapnic dogs. Pimobendan dose-dependently increased CO in eucapnia (baseline: 3.6 ± 0.2 L/kg/m 2 [mean ± SE], low: 5.0 ± 0.4 L/kg/m 2 , high: 5.8 ± 0.5 L/kg/m 2 , P < 0.001) and hypercapnia (baseline: 4.9 ± 0.5 L/kg/m 2 , low: 5.8 ± 0.5 L/kg/m 2 , high: 6.2 ± 0.5 L/kg/m 2 , P < 0.001), and increased HR and decreased SVR and PVR under both conditions (P < 0.001). In hypercapnia, the degree of increase or decrease of these cardiovascular measurements (except for PAP) by pimobendan was less than that in the eucapnic dogs., Conclusions: Pimobendan maintains function as an inodilator in anesthetized dogs with induced respiratory acidosis., (© Veterinary Emergency and Critical Care Society 2022.)

Purpose of Review: Respiratory acidosis is commonly present in patients with respiratory failure. The usual treatment of hypercapnia is to increase ventilation. During the recent surge of COVID-19, respiratory acidosis unresponsive to increased mechanical ventilatory support was common. Increasing mechanical ventilation comes at the expense of barotrauma and hemodynamic compromise from increasing positive end-expiratory pressures or minute ventilation. Treating acute respiratory acidemia with sodium bicarbonate remains controversial., Recent Findings: There are no randomized controlled trials of administration of sodium bicarbonate for respiratory acidemia. A recent review concluded that alkali therapy for mixed respiratory and metabolic acidosis might be useful but was based on the conflicting and not conclusive literature regarding metabolic acidosis. This strategy should not be extrapolated to treatment of respiratory acidemia. Low tidal volume ventilation in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) has beneficial effects associated with permissive hypercapnia. Whether the putative benefits will be negated by administration of alkali is not known. Hypercapnic acidosis is well tolerated, with few adverse effects as long as tissue perfusion and oxygenation are maintained., Summary: There is a lack of clinical evidence that administration of sodium bicarbonate for respiratory acidosis has a net benefit; in fact, there are potential risks associated with it., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Alkali therapy for certain organic acidoses remains a topic of ongoing controversy, but little attention has been given to a related medical controversy, namely the prescription of alkali for respiratory acidosis. We first describe the determinants of carbon dioxide retention in the 2 types of respiratory failure; hypercapnic respiratory failure and hypoxemic respiratory failure with coexisting hypercapnia. We then highlight the deleterious consequences of severe acidemia for several organ systems, particularly the cardiovascular and central nervous systems. We argue that alkali therapy is not indicated for respiratory acidosis as a simple acid-base disturbance. Notwithstanding, we recommend prescription of alkali for severe acidemia caused by mixed acidosis (ie, combined respiratory and metabolic acidosis) or permissive hypercapnia. We examine the utility of alkali therapy in various clinical scenarios incorporating respiratory acidosis. We conclude that controlled studies will be required to test the impact of alkali therapy on clinical outcomes of these clinical settings. Such studies should also examine the optimal mode of administering alkali (amount, rate, and tonicity) and the blood pH to be targeted. The development of new buffers should be explored, especially systems that do not generate carbon dioxide or even consume it., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

In acidosis, catecholamines are attenuated, and higher doses are often required to improve cardiovascular function. Colforsin activates adenylate cyclase in cardiomyocytes without beta-adrenoceptor. Here, six beagles were administered colforsin or dobutamine four times during eucapnia (partial pressure of arterial carbon dioxide 35-40 mm Hg; normal) and hypercapnia (ibid 90-110 mm Hg; acidosis) conditions. The latter was induced by CO2 inhalation. Anesthesia was induced with propofol and maintained with isoflurane. Cardiovascular function was measured by thermodilution and a Swan-Ganz catheter at baseline and 60 min after 0.3 μg/kg/min (low), 0.6 μg/kg/min (middle), and 1.2 μg/kg/min (high) colforsin administration. The median pH was 7.38 [range 7.33-7.42] and 7.01 [range 6.96-7.08] at baseline in the Normal and Acidosis conditions, respectively. Endogenous adrenaline and noradrenaline levels at baseline were significantly (P < 0.05) higher in the Acidosis than in the Normal condition. Colforsin induced cardiovascular effects similar to those caused by dobutamine. Colforsin increased cardiac output in the Normal condition (baseline: 3.9 ± 0.2 L/kg/m2 [mean ± standard error], low: 5.2 ± 0.4 L/kg/min2, middle: 7.0 ± 0.4 L/kg/m2, high: 9.4 ± 0.2 L/kg/m2; P < 0.001) and Acidosis condition (baseline: 6.1 ± 0.3 L/kg/m2, low: 6.2 ± 0.2 L/kg/m2, middle: 7.2 ± 0.2 L/kg/m2, high: 8.3 ± 0.2 L/kg/m2; P < 0.001). Colforsin significantly increased heart rate and decreased systemic vascular resistance compared to values at baseline. Both drugs increased pulmonary artery pressure, but colforsin (high: 13.3 ± 0.6 mmHg in Normal and 20.1 ± 0.2 mmHg in Acidosis) may have lower clinical impact on the pulmonary artery than dobutamine (high: 19.7 ± 0.6 in Normal and 26.7 ± 0.5 in Acidosis). Interaction between both drugs and experimental conditions was observed in terms of cardiovascular function, which were similarly attenuated with colforsin and dobutamine under acute respiratory acidosis., Competing Interests: The authors have declared that no competing interests exist.

Objective: To establish rat model of lung ischemia/reperfusion (IR) in vivo, and to explore the effects of acidification pretreatment for respiratory acidosis on the expression of matrix metalloproteinase-9 (MMP-9) and the possible mechanisms.
 Methods: A total of 36 male Sprague-Dawley rats were divided into a sham group (S group), a IR group, and an experiment group (RA group) (n=12 in each group). The rat left lung hilum in the S group was dissociated, followed by perfusion without ischemia. After the left lung hilum in the IR group was blocked for 45 min, the rats were followed by reperfusion for 180 min. After left lung hilum in the RA group was dissociated, the respiratory parameters were adjusted so that pressure of end tidal carbon dioxide (PETCO2) reached 56-65 mmHg (1 mmHg=0.133 kPa) for 5 min, then the rats was subjected to IR. Lung tissue wet/dry (W/D) and lung permeability index (LPI) were calculated, while the lung histopathology was observed and the MMP-9 protein expression were measured.
 Results: Compared with the control group, the W/D and LPI in the IR group and the RA group increased after reperfusion (both P<0.05), and the levels of W/D and LPI in the group RA were lower than that in the IR group (P<0.05). LPI and pathology scores were significantly lower in the RA group than those in the IR group (both P<0.01). After IR, the expression of MMP9 in the lung tissues in the IR group and the RA group increased significantly (both P<0.01). The expression of MMP-9 protein in the RA group was significantly lower than that in the IR group (P<0.01).
 Conclusion: After lung IR injury, the expression of MMP-9 protein, vascular permeability and inflammatory exudation is increased. The acidification pretreatment for respiratory acidosis can inhibit the expression of MMP-9 protein and reduce inflammatory exudation after lung IR, showing a protective effect on lung IR injury.

Background: Critical central airway obstruction (CAO) requires emergent airway intervention, but current guidelines lack specific recommendations for airway management in the emergency department (ED) while awaiting rigid bronchoscopy. There are few reports of the use of noninvasive ventilation (NIV) in tracheomalacia, but its use as a temporizing treatment option in fixed, malignant CAO has not, to the best of our knowledge, been reported., Case Report: An 84-year-old woman presented to the ED in respiratory distress, too breathless to speak and using her accessory muscles of respiration, with bilateral rhonchi throughout the lung fields. Point-of-care arterial blood gas revealed severe hypercapnia, and NIV was initiated to treat a presumed bronchitis with hypercapnic respiratory failure. Chest radiography revealed a paratracheal mass with tracheal deviation and compression. A diagnosis of critical CAO was made. While arranging for rigid bronchoscopic stenting, the patient was kept on NIV to good effect. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Recommendations for emergent treatment of life-threatening, critical CAO before bronchoscopic intervention are not well established. Furthermore, reports of NIV use in CAO are rare. We suggest that emergency physicians consider NIV as a temporizing measure for critical CAO while awaiting availability of bronchoscopy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Acidification of blood entering a membrane lung (ML) with lactic acid enhances CO2 removal (VCO2ML). We compared the effects of infusion of acetic, citric, and lactic acids on VCO2ML. Three sheep were connected to a custom-made circuit, consisting of a Hemolung device (Alung Technologies, Pittsburgh, PA), a hemofilter (NxStage, NxStage Medical, Lawrence, MA), and a peristaltic pump recirculating ultrafiltrate before the ML. Blood flow was set at 250 ml/min, gas flow (GF) at 10 L/min, and recirculating ultrafiltrate flow at 100 ml/min. Acetic (4.4 M), citric (0.4 M), or lactic (4.4 M) acids were infused in the ultrafiltrate at 1.5 mEq/min, for 2 hours each, in randomized fashion. VCO2ML was measured by the Hemolung built-in capnometer. Circuit and arterial blood gas samples were collected at baseline and during acid infusion. Hemodynamics and ventilation were monitored. Acetic, citric, or lactic acids similarly enhanced VCO2ML (+35%), from 37.4 ± 3.6 to 50.6 ± 7.4, 49.8 ± 5.6, and 52.0 ± 8.2 ml/min, respectively. Acids similarly decreased pH, increased pCO2, and reduced HCO3 of the post-acid extracorporeal blood sample. No significant effects on arterial gas values, ventilation, or hemodynamics were observed. In conclusion, it is possible to increase VCO2ML by more than one-third using any one of the three metabolizable acids.

Objective: To determine the usefulness of non-invasive ventilation (NIV) in elderly patients (≥75) admitted to a respiratory monitoring unit (RMU) during hospitalization and 1 year later in comparison with the results from the younger age group (<75)., Material and Methods: Ours is a prospective observational study carried out at the Hospital Universitario La Princesa (Madrid, Spain). We recruited all patients who were ≥75 years old and were admitted to our RMU during the period 2008-2009 with respiratory acidosis (pH<7.35 and PaCO(2)>45 mmHg) requiring NIV. We gathered data for basic variables as well as sociodemographics, history of previous pathologies, reason for hospitalization and severity, analysis upon admission and the evolution of blood gases at the start of NIV (within the first hour and after 24 h), complications and evolution at the 1-year follow-up., Results: Mean age of the sample was 80.6. The Charlson index was 3.27. About half of the patients had some limitation for performing daily activities. The main reasons for admission were COPD exacerbation and heart failure. There were complications in 36% of the cases (11 renal failure and 6 atrial fibrillation). The survival rate at the 1-year follow-up was 63.21%., Conclusions: NIV is a good alternative in elderly patients admitted to the hospital with respiratory acidosis. We did not detect differences in mortality during admission between the two groups. The elderly patients were more frequently re-admitted than the younger group in the 6-12 months after hospital discharge. This could be due to their poorer functional state after hospitalization requiring NIV., (Copyright © 2012 SEPAR. Published by Elsevier España, S.L. All rights reserved.)

Background: Birth asphyxia is characterized by intermittent periods of hypoxia/ischemia leading to metabolic acidosis. The use of intravenous sodium bicarbonate (IVSB) is still a matter of controversy in clinical practice., Objective: To assess the use of IVSB in birth asphyxia by attending neonatologists in European hospitals., Design/methods: Survey using a questionnaire administered to neonatologists in Europe whose electronic addresses were provided by the national councils of neonatology of each participating country. The questionnaire consisted of a brief theoretical introduction followed by demographic questions related to the respondent's professional qualification. This was followed by a clinical case of an asphyxiated term neonate with severe combined metabolic and respiratory acidosis and case-specific questions related to the perceived indication for administration of IVSB and use of additional therapies to address the clinical situation. Descriptive statistics and χ² analysis were performed., Results: The questionnaire was answered by 259 neonatologists from 17 countries. IVSB was believed to be indicated by 109 (42.2%) of the respondents in this clinical scenario. Results differed significantly between countries, with IVSB use varying from as high as 68% in Portugal and <5% in Scandinavian countries. However, there were no differences in the choice of other therapeutic measures., Conclusions: Although scientific evidence suggests that IVSB is not effective in asphyxiated newborns and current guidelines do not recommend its use, 42.2% of the consulted neonatologists in Europe would use it, with significant differences between but not within countries. There were no differences regarding additional measures to overcome asphyxia. Strategies to implement use of internationally accepted guidelines are needed., (Copyright © 2010 S. Karger AG, Basel.)

Background: Drug treatments for acute cardiogenic pulmonary oedema (ACPO) have not been rigorously evaluated and recent observational data suggests some agents are related to poorer outcome., Aim: We aimed to examine the effect of treatment with diuretics, nitrates and opiates on 7-day mortality, acidosis and respiratory distress in UK Emergency Department (ED) patients with severe acidotic pulmonary oedema., Design: Analysis of data from the 3CPO trial; a multicentre randomized controlled trial., Methods: Data were analysed from patients recruited with severe acidotic pulmonary oedema to the 3CPO trial in 26 UK EDs between 2003 and 2007. The effects of these treatments on 7-day mortality, improvement in acidosis (pH change between baseline and 1 h) and improvement in respiratory distress (patient measured breathlessness using a Visual Analogue Score between baseline and 1 h) were tested using univariate logistic regression analysis, and a regression model used to adjust for confounding baseline differences., Results: Nitrates were given to 947/1048 (90.4%) patients, diuretics to 934/1049 (89.0%) patients and opiates to 541/1052 patients (51.4%). Adjusted analysis showed that opiate treatment was associated with less improvement in acidosis [difference in improvement in pH -0.022, 95% confidence interval (CI) -0.014 to -0.030, P < 0.001], but no difference in mortality or improvement in respiratory distress. We found no evidence that nitrate or diuretic use were associated with any difference in mortality, improvement in acidosis or respiratory distress., Conclusion: Opiate use is associated with less improvement in acidosis during initial treatment and may attenuate effective treatment of severe acidotic ACPO.

Objective: To determine the effectiveness of artificial surfactant therapy using KL-4 surfactant in newborn pigs with hydrochloric acid (HCl)-induced acute lung injury (ALI)., Design: After induction of ALI via intratracheal HCl instillation, pigs were randomized to receive 5.8 ml/kg KL-4 surfactant or no surfactant prior to extubation to bubble CPAP., Setting: Clinical laboratory., Subjects: Spontaneously breathing newborn pigs (<1 week of age)., Interventions: Treatment with KL-4 surfactant on bubble CPAP with PEEP of 6 cmH(2)O for 3.5 hr after extubation compared with controls., Measurements: Physiologic parameters and arterial blood gases were measured every 15 min. At the conclusion of the study, the lungs were excised for the analysis of histopathology and morphometric data., Main Results: Pigs treated with KL-4 surfactant had arterial blood gases with less acidosis (P < 0.001), higher P(a)O(2) levels (P < 0.001), and lower P(a)CO(2) levels (P < 0.001). Pigs treated with KL-4 surfactant had improved survival compared with controls (6/12 KL-4, 2/12 control, P < 0.05). Postmortem morphometric data demonstrated that pigs treated with KL-4 surfactant had larger (P < 0.05) exchange units in the caudal-dorsal lung as compared to relatively atelectatic region in the control animals., Conclusions: In newborn pigs with severe HCl-induced ALI, treatment with KL-4 surfactant resulted in improved respiratory parameters, less dependent atelectasis, and improved short-term survival., (Copyright 2010 Wiley-Liss, Inc.)

Objective: Prolonged hypercapnia is commonly encountered during the treatment of acute respiratory distress syndrome and acute respiratory failure attributable to other causes with protective ventilation strategies. In these circumstances, compensatory renal buffering returns pH to normal establishing a condition of buffered hypercapnia. It is also common intensive care practice to correct the pH more rapidly using bicarbonate infusions. Although it is well-established that hypercapnic acidosis has potent anti-inflammatory and protective effects, the effect of buffered hypercapnia on acute lung injury and acute respiratory distress syndrome is unknown. We therefore wished to determine the effects of buffered hypercapnia on acute lung injury induced by endotoxin or Escherichia coli infection in vivo., Design: Prospective, randomized animal study., Setting: University research laboratory., Subjects: Adult male Sprague-Dawley rats., Interventions: We established buffered hypercapnia by exposing rats to a hypercapnic environment for 3 days before the induction of lung injury. Buffered hypercapnia rats (initial pH >7.35, FiCO2 = 0.05) and normocapnic controls (initial pH >7.35, FiCO2 = 0.00) were then anesthetized, mechanically ventilated, and lung injury induced by intra-tracheal inoculation of endotoxin (series I) or Escherichia coli (series II)., Measurements and Main Results: Buffered hypercapnia significantly increased both endotoxin and Escherichia coli-induced lung injury when compared to normocapnic controls, as assessed by arterial oxygenation, lung compliance, pro-inflammatory pulmonary cytokine concentrations, and measurements of structural lung damage. In additional in vitro experiments buffered hypercapnia did not alter neutrophil phagocytosis ability but did impaired epithelial wound healing., Conclusions: Our results demonstrate that infection-induced injury in vivo is worsened after renal buffering of hypercapnic acidosis independently of any changes in tidal volume. These findings have important implications for our understanding of the pathogenesis of infection-induced lung injury during the use protective ventilation strategies that permits buffered hypercapnia and during infective exacerbations of chronic lung diseases associated with sustained hypercapnia.

We report the case of a severe acute asthma, which required, after optimal medical therapy, helium and sevoflurane CO-administration after tracheal intubation. The Anesthetic Conserving Device allowed sevoflurane use with intensive care unit's ventilator. The helium-sevoflurane association was maintained during 9 days to decrease the bronchospasm, waiting for the efficiency of an aetiologic treatment. We discuss the suitability of this association to treat severe acute asthma, and its administration modalities.

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.

Objective: To determine concentrations of electrolytes, total bilirubin, urea, creatinine, and hemoglobin; activities of some enzymes; and Hct and number of leukocytes and erythrocytes of newborn calves in relation to the degree of acidosis and treatment with a hypertonic sodium bicarbonate (NaHCO(3)) solution., Animals: 20 acidotic newborn calves with a blood pH < 7.2 and 22 newborn control calves with a blood pH > or = 7.2., Procedures: Approximately 10 minutes after birth, acidotic calves were treated by IV administration of 5% NaHCO(3) solution. The amount of hypertonic solution infused was dependent on the severity of the acidosis., Results: Treatment resulted in a significant increase in the mean +/- SEM base excess from -8.4 +/- 1.2 mmol/L immediately after birth to 0.3 +/- 1.1 mmol/L 120 minutes later. During the same period, sodium concentration significantly increased from 145.3 +/- 0.8 mmol/L to 147.8 +/- 0.7 mmol/L. Mean chloride concentration before NaHCO(3) administration was significantly lower in the acidotic calves (99.6 +/- 1.1 mmol/L) than in the control calves (104.1 +/- 0.9 mmol/L). Calcium concentration in acidotic calves decreased significantly from before to after treatment. Concentrations of potassium, magnesium, and inorganic phosphorus were not affected by treatment., Conclusions and Clinical Relevance: Administration of hypertonic NaHCO(3) solution to acidotic neonatal calves did not have any adverse effects on plasma concentrations of several commonly measured electrolytes or enzyme activities. The treatment volume used was smaller, compared with that for an isotonic solution, which makes it more practical for use in field settings.

In rats with experimental thiopental coma rectal temperature decreased by 9.4 degrees C, oxygen consumption 5-fold, and arteriovenous Po(2)gradient decreased 2-fold within 3 h; CO(2)accumulated in the blood and mixed type acidosis developed. Administration of sodium succinate under these conditions increased arteriovenous Po(2)gradient and reduced manifestations of metabolic acidosis. Maintenance of normal body temperature (warming) corrected primarily manifestations of respiratory acidosis. Each therapeutic agent reduced inhibition of O(2)consumption by 1/4; animal survival tended to increase from 42 to 50%. Combined use of these treatments potentiated the antiacidotic effect and increased survival to 92%. The authors conclude that hypothermia inhibits the therapeutic effect of succinate in barbiturate coma.

Bicarbonate infusion is traditionally used to increase pH during metabolic acidosis, but it has been also suggested to increase the pH during permissive hypercapnia. In this paper we will discuss the physicochemical effect of adding (Na+ HCO3-), first in a closed system (venous blood) and then in an open system (the blood after the lung). According to Stewart model, in the closed system two independent variables are changed (CO2 and strong ion difference). As a first result changes in pH are negligible. If the CO2 is cleared by the lung and the PCO2 is maintained as before the infusion, the rise in pH is due to the SID increase caused by the (Na+) rise. The effect is independent on (HCO3-) infusion and equivalent to adding (Na+ OH-) instead of (Na+ HCO3-).

We describe a case of prolonged severe hypercapnia with respiratory acidosis occurring during an episode of near-fatal asthma in an 8-year-old boy, followed by complete recovery. After admission to the intensive care unit, despite treatment with maximal conventional bronchodilatative therapy, the clinical picture deteriorated with evident signs of respiratory muscle fatigue. The child was sedated, intubated and mechanically ventilated. Magnesium sulphate, ketamine and sevoflurane were gradually introduced together with deep sedation, curarization and continuous bronchodilatative therapy. Ten hours after admission, arterial pCO2 reached 39 kPa (293 mmHg), pH was 6.77 and pO2 8.6 kPa (65 mmHg). Chest radiograph showed severe neck subcutaneous emphysema, with signs of mediastinal emphysema. No episode of haemodynamic instability was seen despite severe prolonged hypercapnia lasting more than 14 h. Oxygenation was maintained and successful recovery followed without neurological or cardiovascular sequelae. This case shows the cardiovascular and neurological tolerance of a prolonged period of supercarbia in a paediatric patient. The most important lesson to be learned is the extreme importance of maintaining adequate tissue perfusion and oxygenation during an asthma attack. The second lesson is that when conventional bronchodilators fail, the intensivist may resort to the use of drugs such as ketamine, magnesium sulphate and inhalation anaesthesia. In this context deep sedation and curarization are important not only to improve oxygenation, but also to reduce cerebral metabolic requirements., (Copyright 2004 Blackwell Publishing Ltd)

Respiratory activity is under circadian modulation and the physiological mechanisms may involve the pineal secretory product, melatonin, and the carotid chemoreceptor. We hypothesized that melatonin modulates the carotid chemoreceptor response to hypercapnic acidosis. To determine whether the effect of melatonin on the chemoreceptor response to hypercapnic acidosis is mediated by melatonin receptors in the chemosensitive cells, cytosolic calcium ([Ca2+]i) was measured by spectrofluorometry in fura-2-loaded glomus cells dissociated from rat carotid bodies. Melatonin (0.01-10 nm) per se did not change the [Ca2+]i levels of the glomus cells but it concentration-dependently attenuated the peak [Ca2+]i response to hypercapnic acidosis in the glomus cells. In addition, the [Ca2+]i response was attenuated by 2-iodomelatonin, an agonist of melatonin receptors. The melatonin-induced attenuation of the [Ca2+]i response to hypercapnic acidosis was abolished by pretreatment with an non-selective mt1/MT2 antagonist, luzindole, and by MT2 antagonists, 4-phenyl-2-propionamidotetraline or DH97. In situ hybridization study with antisense mt1 and MT2 receptor mRNA oligonucleotide probes showed an expression of mt1 and MT2 receptors in the rat carotid body. Also, melatonin attenuated the carotid afferent response to hypercapnic acidosis in single- or pauci-fibers recorded from the sinus nerve in isolated carotid bodies superfused with bicarbonate-buffer saline. Results suggest that an activation of the melatonin receptors expressed in the glomus cells of the rat carotid body reduces the chemoreceptor response to hypercapnic acidosis. This modulation may play a physiological role in the influence of the circadian rhythms on the chemoreflex.

Despite the lack of evidence for its effectiveness in the treatment of acid-base disturbances in critically ill patients of all ages, and despite several lines of evidence that indicate it might be dangerous, bicarbonate therapy is used routinely in many neonatal intensive care units. The justification for the persistent use of this controversial therapy comes from a variety of sources, many based more in philosophy than in science. Clinicians contemplating the use of bicarbonate therapy should consider what they expect the intervention to accomplish and what evidence exists that their therapeutic objective will be met. Without rigorous scientific support for this therapy, it should be considered of unproven value and, therefore, experimental.

Severe coagulation defects often develop in neonates undergoing cardiac surgery, both as a result of the surgical intervention, and as pre-existing defects in the hemostatic mechanisms. The following case report describes a newborn patient with complex congenital heart disease and respiratory failure whose pre-operative coagulopathy was aggressively managed prior to surgical correction. A 5-day-old, 2.5 kg child presented with interrupted aortic arch, ventricular septal defect, atrial septal defect, and patent ductus arteriosus. On admission, he was in respiratory arrest suffering from profound acidemia. In addition, the child was hypothermic (30.1 degrees C), septic (Streptococcus viridans), and coagulopathic (disseminated intravascular coagulation-DIC). The patient was immediately intubated and initial coagulation assessment revealed the following: prothrombin time (PT) 48.9 s (international normalized ratio (INR) 15.7), activated partial thromboplastin time (aPTT) >106 s, platelet count 30,000 mm(3), fibrinogen 15 mg dL(-1) and antithrombin III (AT-III) 10%. Before cardiac surgery could be performed, the patient's DIC was corrected with the administration of cryoprecipitate (15 ml), fresh frozen plasma (300 ml), and platelets (195 ml). In spite of the large transfusion of fresh frozen plasma, the AT-III activity, measured as a percentage, remained depressed at 33. Initial thromboelastographic (TEG) determination revealed an index of +2.02, and following 100 IU administration of an AT-III concentrate, declined to -2.32. Sequential TEG profiles were performed over several days, with the results used to guide both transfusion and medical therapy. The congenital heart defect correction was subsequently performed with satisfactory initial results, but the patient developed a fungal infection and expired on the 16th post-operative day. The present case describes techniques of coagulation management for a newborn with both a severe hemostatic defect and congenital heart disease.

Background: Metabolic alkalosis usually complicates the evolution of patients with hypercapnia under diuretic or steroid therapy. The objective of this study was to analyze the efficiency of therapy with acetazolamide, a reversible carbonic anhydrase inhibitor, in this condition., Patients and Methods: Prospective study conducted at our hospital from June 1994 to March 1996, with 45 patients who had chronic respiratory acidosis and metabolic alkalosis. After a previous stabilization of the patient and eventually the discontinuation of diuretic or corticosteroid drugs fro 24-48 hours, 500 or 750 mg of acetazolamide were administered daily for 48 hours. Later, variations both in arterial gasometry and venous electrolytes were analyzed by comparing two means of paired data., Results: After therapy with acetazolamide a clinical improvement was observed in patients, a decrease in PaCO2, pH and CO3H (p < 0.001) and an increase in PaO2 (p < 0.001). Hypochloremia (82.2%) and hypopotassemia (33.3%) were the most common electrolytic abnormalities before therapy. Both abnormalities improved significantly after the administration of acetazolamide. In five patients (11.1%) acetazolamide was discontinued when metabolic acidosis appeared, which only in three cases was associated with acidemia. No secondary effects were observed., Conclusions: Acetazolamide is an efficient alternative for treatment of patients with respiratory acidosis and metabolic alkalosis, particularly when other more common measures in this condition (discontinuation of diuretics and/or volemic replacement) have failed or are contraindicated. On the other hand, the emergence of relevant secondary effects is unlikely.

Objective: Status asthmaticus with respiratory failure is a potentially fatal complication of bronchial asthma. To prevent a fatality in status asthmaticus with respiratory failure, treatment with intravenous isoproterenol or mechanical ventilation has been advocated. These interventions also have serious potential complications, however, and while continuous inhalation of beta agonists has shown promise, the optimal therapy of severe status asthmaticus remains unclear. This paper describes our experience with a treatment protocol used in status asthmaticus with respiratory failure that seeks to avoid intravenous isoproterenol or assisted ventilation., Study Design: Case series of pediatric intensive care patients with severe respiratory failure due to status asthmaticus. Six children and adolescents experienced a total of nine episodes of severe respiratory failure due to status asthmaticus., Results: In seven of the nine episodes the patients were managed without either intravenous isoproterenol or mechanical ventilation. Hypercarbia persisted for an average of 25 hours (range 17 to 40 hours) in these seven episodes. All subjects recovered without notable sequelae. In two episodes, clinical and blood gas deterioration led to mechanical ventilation. Ventilation was required for 112 and 42 hours, respectively, in these episodes and the patients developed either pneumothorax or pneumomediastinum during ventilation., Conclusion: Using a protocol initiated in 1978 for correction of hypoxia and acidemia, many patients with severe respiratory failure from status asthmaticus can be treated without isoproterenol or mechanical ventilation. Since those treatments have significant risks, consideration should be given to this intervention before resorting to them.

A 28-year-old woman in status asthmaticus and respiratory acidemia refused orotracheal intubation and mechanical ventilation in the emergency department. In view of this situation, a mixture of helium-oxygen gas (heliox) was initiated with a nonrebreathing oxygen mask. Within 2 hours of treatment, the patient's respiratory acidemia had been corrected, and heliox inhalation therapy was discontinued without further incident.

Objective: To investigate the effects of infusion of dopexamine hydrochloride, a new synthetic catecholamine, on cardiopulmonary status and urine output in neonates with respiratory and circulatory failure., Design: Prospective clinical study with each patient serving as his own control., Setting: Intensive care unit (14 beds) in a 300-bed paediatric teaching hospital., Patients: Seventeen neonates with low birth weight (LBW) requiring mechanical ventilation in the first 4 days of life, who initially had two of the following symptoms: hypotension, oliguria, metabolic acidosis with base deficit >10 and failure to respond to volume loading., Interventions: Cardiopulmonary variables, diuresis and acid-base status were measured before and after volume loading, in patients who did not improve infusion of dopexamine was started at a dose of 2 microg kg-1 min-1 which was titrated to achieve blood pressure, urine output, and base deficit in normal range. Observations were continued for a period of 5 h., Measurements and Results: Systolic blood pressure increased significantly after 3 h. of dopexamine infusion and remained elevated up to the end of the study period. Diastolic and mean blood pressure increased slightly (NS). Diuresis increased significantly from the 4th h of dopexamine infusion. Arterial blood pH increased significantly from baseline at 5 h after the start of dopexamine administration. There was also a significant improvement in the PtcO2/PaO2 index., Conclusion: In neonates with respiratory and circulatory failure, dopexamine increases blood pressure and improves arterial pH and urine output.

The effects of 1M sodium bicarbonate (NaHCO3) on cardiac function and myocardial metabolism during hypoxia were compared with those of 1M sodium chloride (NaCl) in anesthetized dogs. Metabolic acidosis was induced with inhalation of low fraction of oxygen (9%) for 2 hours. NaHCO3 (n = 9) or NaCl (n = 10) was infused intravenously in a half dose of 0.2 x body weight x base excess mEq in 30 seconds. This treatment was repeated five minutes later. In NaHCO3 group; with first infusion, both blood and intramyocardial pH increased. Left ventricular pressure (LVP) and maximum rate of rise of LVP (LV dP/dt max) were unchanged. Cardiac index (CI) tended to increase, while left ventricular end-diastolic pressure (LVEDP) and LVEDP/LVP increased significantly. In five dogs in which myocardial glucose uptake increased, LV dP/dt max increased. With the second infusion, inspite of the increase of blood and intramyocardial pH, LVP and LV dP/dt max decreased significantly compared with the preceding values. In NaCl group, with first infusion, blood and intramyocardial pH decreased. CI increased significantly, while LVP and LV dP/dt max tended to decrease, and LVEDP and LVEDP/LVP increased significantly. After the second infusion, myocardial contractility was depressed significantly. In both groups, blood lactate (LA) level increased significantly, especially with NaHCO3 infusion. LV dP/dt max correlated significantly with LA in NaCl group (r = -0.614, P < 0.001). However, in NaHCO3 group, LV dP/dt max did not correlate with LA. Blood glucose level (r = 0.612, P < 0.001) and myocardial glucose uptake (r = 0.718, P < 0.001) correlated significantly with LV dP/dt max in NaHCO3 group.(ABSTRACT TRUNCATED AT 250 WORDS)

Sodium bicarbonate has been thought to be effective for hypoxic lactic acidosis, but recently its adverse reactions have been pointed out. Therefore, the effects of NaHCO3 therapy in hypoxic lactic acidosis were evaluated in the anesthetized dog. Studies were carried out in four groups of adult mongrel dogs. The first group received control ventilation with hypoxic gas (5%O2 + 95%N2) and NaHCO3 therapy to adjust blood base excess. The second group did not receive NaHCO3 therapy after control ventilation with hypoxic gas. The third group breathed hypoxic gas spontaneously and received NaHCO3 therapy. The fourth group did not receive NaHCO3 therapy during spontaneous breathing of hypoxic gas. The changes of acid-base balance, CO2 and lactate of arterial blood and cerebrospinal fluid (CSF) were analysed in each dog. The conclusions were as follows; 1. The NaHCO3 therapy is not necessary for hypoxic lactic acidosis under proper ventilation, if arterial blood pH does not fall extremely. 2. The CSF acid-base balance is kept within normal ranges, so that the NaHCO3 therapy is not necessary from this point of view.

To understand the cardiovascular response to respiratory acidosis, we measured hemodynamics, left ventricular pressure, and left ventricular volume (three ultrasonic crystal pairs) during eucapnia and respiratory acidosis in 10 fentanyl-anesthetized open-chest dogs. Left ventricular contractility was assessed primarily by measuring the slope (Emax) and intercept (V0) of the left ventricular end-systolic pressure-volume relation determined by combining end-systolic points from a vena caval occlusion and from brief aortic cross-clamping. Respiratory acidosis (pH 7.09, Pco2 92 mm Hg) reduced contractility by a decrease in Emax (11.4 to 9.2 mm Hg/ml, p less than 0.01) with no change in V0. Despite this, cardiac output increased (1.7 to 2.1 l/min, p less than 0.01), and heart rate increased (96 to 121 beats/min, p less than 0.05), with no change in blood pressure. Systemic vascular resistance fell by 26% (p less than 0.01). During eucapnia, propranolol reduced Emax (11.4 to 4.6 mm Hg/ml, p less than 0.01) with no change in V0. After propranolol treatment, respiratory acidosis further reduced Emax (4.6 to 3.6 mm Hg/ml, p less than 0.05) and increased end-systolic volume more than before propranolol (p less than 0.001). Now cardiac output did not increase even though heart rate increased (81 to 106 beats/min, p less than 0.001) and systemic vascular resistance fell by 20% (p less than 0.01). We conclude that the effect of respiratory acidosis on the circulation is to increase venous return (equals cardiac output) in the face of decreased left ventricular contractility. The beta-adrenergic response to respiratory acidosis substantially ameliorated the increase in end-systolic volume and supported the increase in venous return but did not alter the associated tachycardia or vasodilation. Respiratory acidosis, like propranolol treatment, decreases contractility by decreasing Emax.

Nineteen infants with acidosis associated with RDS were studied following the infusion of: (1) 0.58M (7%) THAM over 30 seconds; (2) molar bicarbonate over 30 seconds; (3) molar bicarbonate over 2 minutes; and (4) molar bicarbonate over 5 minutes. PaC02 fell after THAM; PaC02 rose sharply after bicarbonate and remained elevated 10 minutes after infusion. The pH rose abruptly in all infants and remained significantly elevated 10 minutes after infusion. Pa02 changes were variable; no infant had immediate improvement in Pa02. The changes in osmolality, hematocrit, and colloid osmotic pressure describe the immediate osmotic hemodilution following the infusion of hypertonic base.

The administration of sodium bicarbonate solution, which has been advocated for the treatment of metabolic acidosis, may have detrimental side effects. We evaluated oxyhemoglobin saturation and oxygen tensions in eight anesthetized swine before and after freshwater near-drowning and after a rapid intravenous infusion of 7.5% sodium bicarbonate solution (8 mEq/kg). After freshwater aspiration, arterial and venous oxygen tensions and oxyhemoglobin saturation decreased. Administration of sodium bicarbonate resulted in decreased venous and increased arterial, oxygen tensions. Arterial, but not venous, oxyhemoglobin saturation increased. These findings suggest that sodium bicarbonate caused a distinct leftward shift in the oxyhemoglobin dissociation curve, which could impair tissue oxygenation. Therefore, to avoid detrimental effects, sodium bicarbonate should be administered slowly and in a dose sufficient just to correct metabolic acidosis.

In summary, infusion of bicarbonate in the treatment of neonatal acidosis has limited value. Although it may be useful adjunct in the resuscitation of severely depressed and acidotic infants, its efficacy in the management of postasphyxia acidosis or RDS is not supported by any data. The clear risks and disadvantages of such infusions should warn against its current indiscriminate use.

We have studied the serial changes in arterial blood gases in fourteen patients with acute severe asthma, all of whom received a standard therapeutic regime and had similar measurements made at identical time intervals under standard conditions. Hypoxaemia on admission was a constant finding, and the arterial oxygen tension often took a week or longer to return to a normal level. Treatment with 60% inspired oxygen provided a safe means of relieving hypoxaemia, provided that blood gases were measured before and during oxygen therapy. Most patients had a normal arterial carbon dioxide tension, which indicated the severity of their illness. Acid-base disturbances, when present, were mild and needed no specific treatment. Age, duration of the acute attack, and severity of airways obstruction were all unrelated to the changes in blood gas tension, and pulse rate was found to be a poor predictor of hypoxaemia in elderly asthmatics. Serial measurements of the arterial blood gases should be made in all patients with acute severe asthma.

Carbicarb (Na2CO3 0.33 molar NaHCO3 0.33 molar), a mixture formulated to avoid the objections to sodium bicarbonate therapy, has been compared with 1 mol/L NaHCO3 and 1 mol/L NaCl in the treatment of mixed respiratory and metabolic acidosis (pH 7.17) produced by asphyxia in rats. In clinically appropriate doses, intravenous NaHCO3 raised arterial pH only 0.03 unit, elevated arterial carbon dioxide pressure, and doubled lactate concentration. With Carbicarb, the pH rise was three times as great and the blood lactate level was unchanged. The new drug should be effective in treating the acidosis of cardiopulmonary failure without raising blood carbon dioxide pressure or lactate levels and at lower sodium doses than required for NaHCO3.