Acute sodium bicarbonate administration improves ventilatory efficiency in experimental respiratory acidosis: clinical implications.

Administering sodium bicarbonate (NaHCO3) 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 NaHCO3 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 NaHCO3 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 NaHCO3 infusion was evaluated by examining the ensuing change in PaCO2 and the linear regression of the PaCO2 vs. pH relationship. Strikingly, PaCO2 failed to increase and the ΔPaCO2 vs. ΔpH slope was negative in respiratory acidosis, whereas PaCO2 increased consistently and the ΔPaCO2 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, PaCO2, and pulmonary ventilation. We propose that NaHCO3 infusion improved the ventilatory efficiency of animals with respiratory acidosis, i.e., it decreased their ratio of total pulmonary ventilation to carbon dioxide excretion (VE/VCO2). Such exclusive effect of NaHCO3 infusion in animals with respiratory acidosis might emanate from baseline increased VD/VT (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 NaHCO3 reported in patients with acute respiratory acidosis.

Aminopyridines Restore Ventilation and Reverse Respiratory Acidosis at Late Stages of Botulism in Mice.

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 CO2, 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.

Sodium bicarbonate therapy for acute respiratory acidosis.

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.

Alkali Therapy for Respiratory Acidosis: A Medical Controversy.

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.

Noninvasive Ventilation as a Temporizing Measure in Critical Fixed Central Airway Obstruction: A Case Report.

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.

[Effects of acidification pretreatment for respiratory acidosis on the expression of matrix metalloproteinase-9 in rat lung tissues following ischemia/reperfusion].

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.

Sevoflurane inhalation for severe bronchial obstruction in infants with bronchiolitis.

Bronchiolitis is a lower respiratory tract viral infection which may result in severe bronchial obstruction and respiratory failure despite treatment with beta-adrenergic agonists and glucocorticoids. Here we describe two otherwise healthy infants with severe bronchiolitis whose clinical course was complicated by marked bronchial obstruction and respiratory acidosis refractory to conventional medications (ß-stimulants, anticholinergics and corticosteroids) and non-invasive positive pressure ventilation. Sevoflurane inhalation allowed both infants to attain a sustained, clinical improvement in ventilation and one patient to avoid mechanical ventilation. We suggest that sevoflurane inhalation may be a therapeutic option in the treatment of young infants with severe bronchiolitis who respond poorly to conventional therapy.

Cardiovascular effects of intravenous pimobendan in dogs with acute respiratory acidosis.

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 (Paco2 35-40 mm Hg) and hypercapnia (Paco2 90-110 mm Hg). Eucapnia was maintained by positive pressure ventilation and hypercapnia was induced by adding exogenous CO2 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/m2 [mean ± SE], low: 5.0 ± 0.4 L/kg/m2 , high: 5.8 ± 0.5 L/kg/m2 , P < 0.001) and hypercapnia (baseline: 4.9 ± 0.5 L/kg/m2 , low: 5.8 ± 0.5 L/kg/m2 , high: 6.2 ± 0.5 L/kg/m2 , 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.

Infection-induced lung injury is worsened after renal buffering of hypercapnic acidosis.

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.

Cardiovascular effects of intravenous colforsin in normal and acute respiratory acidosis canine models: A dose-response study.

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.

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

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

Effects of hypertonic sodium bicarbonate solution on electrolyte concentrations and enzyme activities in newborn calves with respiratory and metabolic acidosis.

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.

Enhanced Extracorporeal CO2 Removal by Regional Blood Acidification: Effect of Infusion of Three Metabolizable Acids.

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.

Effects of aminophylline on the threshold for initiating ventricular fibrillation during respiratory failure.

Cardiac arrhythmias have frequently been reported in association with respiratory failure. The possible additive role of pharmacologic agents in precipitating cardiac disturbances in patients with respiratory failure has only recently been emphasized. The effects of aminophylline on the ventricular fibrillation threshold during normal acid-base conditions and during respiratory failure were studied in anesthetized open chest dogs. The ventricular fibrillation threshold was measured by passing a gated train of 12 constant current pulses through the ventricular myocardium during the vulnerable period of the cardiac cycle. During the infusion of aminophylline, the ventricular fibrillation threshold was reduced by 30 to 40 percent of the control when pH and partial pressures of oxygen (PO2) and carbon dioxide (CO2) were kept within normal limits. When respiratory failure was produced by hypoventilation (pH 7.05 to 7.25; PC02 70 to 100 mm Hg: P02 20 to 40 mm Hg), infusion of aminophylline resulted in an even greater decrease in ventricular fibrillation threshold to 60 percent of the control level. These experiments suggest that although many factors may contribute to the increased incidence of ventricular arrhythmias in respiratory failure, pharmacologic agents, particularly aminophylline, may play a significant role.

Use of tolazoline in newborn infants with diaphragmatic hernia and severe cardiopulmonary disease. A preliminary report.

Two newborn infants with congenital diaphragmatic hernia, one of whom died, had significant improvement in arterial oxygen tension (Pao2) after intravenous administration of tolazoline (Priscoline) (1 to 2 mg. per kilogram). In both infants, systemic hypotension developed within minutes of administration of the drug and required pharmacologic and hemodynamic intervention. The response to tolazoline was more dramatic in the infant who survived, and his oxygen requirements were significantly reduced after the use of this drug. The infant who died also had a significant response to tolazoline. Tolazoline appears to be an important pharmacologic agent for use in the postoperative care of infants with diaphragmatic hernia and associated hypoxemia and acidosis.

Carbicarb: an effective substitute for NaHCO3 for the treatment of acidosis.

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.

Circulatory and diuretic effects of dopexamine infusion in low-birth-weight infants with respiratory failure.

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.

Alteration of oxygen tension and oxyhemoglobin saturation. A hazard of sodium bicarbonate administration.

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.

Heliox inhalation in status asthmaticus and respiratory acidemia: a brief report.

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.

[Effects of NaHCO3 on cardiac function and metabolism during hypoxic metabolic acidosis--2: Rapid infusion of NaHCO3].

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)