Increase In Arterial pH Research Articles

Acute Effects of Sodium Bicarbonate in Children with Congenital Heart Disease with Biventricular Circulation in Non-cardiac Arrest Situations.

Despite the controversy, sodium bicarbonate is a commonly used medication in critically ill patients of all ages. There is a lack of data on the acute impact on hemodynamic parameters, biomarker indicators of cardiac output, and changes in vasoinotropic support after sodium bicarbonate therapy. In our retrospective study on children with biventricular circulation in pediatric cardiac intensive care unit receiving bicarbonate therapy: we analyzed its effects on arterial blood gases, heart rate, blood pressure (BP), central venous pressures (CVP), cerebral and renal near-infrared spectroscopy (NIRS), changes in vasoinotropic and ventilator changes before and after sodium bicarbonate administration. Thirty-one administrations of sodium bicarbonate in 23 patients with congenital heart disease without residual shunts were analyzed. The average age was 15.4months, weight 7.7kg, and the average bicarbonate dose was 1meq/kg. There was an increase in arterial pH from 7.24 to 7.30 (p = 0.14) and bicarbonate changed from 18 to 20mEq/L (p = 0.23). No clinically significant changes were found in the following parameters: heart rate (141 ± 20.1 to 136 ± 19), systolic BP (84 ± 17 to 86 ± 14mmHg), diastolic BP (48 ± 12 to 49 ± 12mmHg), cerebral NIRS (64 ± 12 to 65 ± 12), renal NIRS (80 ± 10 to 81 ± 7), CVP (9 ± 3 to 10 ± 4mmHg), paCO2 (45 ± 26 to 42 ± 7mmHg), paO2 (143 ± 78 to 127 ± 59mmHg), serum lactate (2.2 ± 2.7 to 3.6 ± 3.8mmol/L), and vasoinotropic score (7.5 ± 5.0 to 7.7 ± 4.7). Outside of a change in serum pH and bicarbonate levels no other significant changes were noted after sodium bicarbonate administration in children with congenital heart disease with fully septated, biventricular circulation. There was no improvement in systemic oxygen delivery.

Mechanisms underlying the stimulatory effect of inhaled sulfur dioxide on vagal bronchopulmonary C-fibres.

Brief inhalation of SO2 of concentration >500p.p.m. triggered a pronounced stimulatory effect on vagal bronchopulmonary C-fibres in anaesthetized rats. This stimulatory effect was drastically diminished by a pretreatment with NaHCO3 that raised the baseline arterial pH, suggesting a possible involvement of acidification of airway fluid and/or tissue generated by inhaled SO2 . The stimulation was completely abolished by pretreatment with antagonists of both acid-sensing ion channels and transient receptor potential vanilloid type-1 receptors, indicating that this effect was caused by acid activation of these cation channels expressed in airway sensory nerves. This conclusion was further supported by the results obtained from studies in isolated rat vagal bronchopulmonary sensory neurones and also in the cough response to SO2 inhalation challenge in awake mice. These results provide new insight into the underlying mechanism of harmful irritant effects in the respiratory tract caused by accidental exposure to a high concentration of SO2 . Inhalation of sulfur dioxide (SO2 ) triggers coughs and reflex bronchoconstriction, and stimulation of vagal bronchopulmonary C-fibres is primarily responsible. However, the mechanism underlying this stimulatory effect is not yet fully understood. In this study, we tested the hypothesis that the C-fibre stimulation was caused by SO2 -induced local tissue acidosis in the lung and airways. Single-unit activities of bronchopulmonary C-fibres in response to inhalation challenges of SO2 (500-1500p.p.m., 10 breaths) were measured in anaesthetized rats. Inhalation of SO2 reproducibly induced a pronounced and sustained stimulation (lasting for 15-60s) of pulmonary C-fibres in a concentration-dependent manner. This stimulatory effect was significantly attenuated by an increase in arterial pH generated by infusion of sodium bicarbonate (NaHCO3 ), and completely abrogated by a combined pretreatment with amiloride (an antagonist of acid-sensing ion channels, ASICs) and AMG8910 (a selective antagonist of the transient receptor potential vanilloid type-1 receptor, TRPV1). Furthermore, in isolated rat vagal pulmonary sensory neurones, perfusion of an aqueous solution of SO2 evoked a transient increase in the intracellular Ca2+ concentration; this response was also markedly diminished by a pretreatment with amiloride and AMG8910. In addition, inhalation of SO2 consistently evoked coughs in awake mice; responses were significantly smaller in TRPV1-/- mice than in wild-type mice, and almost completely abolished after a pretreatment with amiloride in TRPV1-/- mice. These results suggested that the stimulatory effect of inhaled SO2 on bronchopulmonary C-fibres was generated by acidification of fluid and/or tissue in the lung and airways, which activated both ASICs and TRPV1 expressed in these sensory nerves.

The use of Arginine Vasopressin in neonates following the Norwood procedure

Following the Norwood palliation, neonates may require an escalation of inotropic and vasoactive support. Arginine Vasopressin may be uniquely useful in supporting this population. A retrospective evaluation of neonates at this institution between November, 2007 and October, 2010 who received Arginine Vasopressin following the Norwood procedure. Data were recorded from the patient records at one hour prior to, and then 1, 2, 3, 4, 6, and 24 hours following Arginine Vasopressin initiation. We included 28 neonates. The mean dose of Arginine Vasopressin was 0.0005 plus or minus 0.0003 units per kilogram per minute. There was an early response (less than 6 hours) characterised by an 8% increase in systolic blood pressure (p = 0.0004), a 100% increase in urine output (p = 0.02), and a 29% decrease in total fluid administration (p = 0.04). The late response (at 24 hours) revealed further increases in systolic blood pressure and urine output as well as a 53% decrease in serum lactate (p = 0.007) and increase in arterial pH from 7.36 to 7.45 (p less than 0.0001). These changes were not accompanied by increases in heart rate or inotrope score. The initiation of Arginine Vasopressin in post-operative Norwood patients was temporally associated with an improvement in markers of perfusion including systolic blood pressure, urine output, lactate, and pH. Further studies are required to ascertain the efficacy of Arginine Vasopressin in this population.

Drotrecogin alfa (activated) for severe sepsis: Could we consider a shorter treatment period in patients with a favorable course?

Purpose The objective of this study was to develop a model to identify patients in whom drotrecogin alfa (activated) (DAA) might be administered for periods shorter than the recommended 96 hours. Methods We did a retrospective chart review of all 124 patients treated with a standard 96-hour infusion of DAA in a 31-bed department of intensive care. Using a stepwise approach, we identified and combined parameters that could help predict outcomes to achieve the best sensitivity associated with 100% specificity. Results Twenty-one (17%) of the 124 patients had a favorable outcome (left the intensive care unit within 5 days of DAA initiation); of these, 11 had an increase in arterial pH in the first 24 hours of treatment compared with 22 (21%) of the 103 patients with intermediate (intensive care unit stay >5 days after DAA initiation) or unfavorable (died within 5 days of DAA initiation) outcomes ( P = not significant). Eight (72.7%) of these 11 patients and no other patient showed a decrease in sequential organ failure assessment score of at least 50% during the first 24 hours ( P < .001). By combining these 2 variables, we could identify, with 100% specificity, 8 of the patients with a favorable outcome (38%) who made a prompt recovery. Conclusions A simple model based on sequential organ failure assessment score and arterial pH can help identify patients with a rapid favorable course in whom a shorter duration of DAA treatment may be justified.

Deep Hypothermia and the Vascular Response to Thiopental

The vascular response to intravenous thiopental in patients on cardiopulmonary bypass during deep hypothermia was examined. This was a prospective observational study. A university teaching hospital. Twenty-one consecutive adult patients undergoing pulmonary thromboendarterectomy during which deep hypothermic circulatory arrest was instituted. Immediately before circulatory arrest, each patient was administered a 500-mg dose of thiopental intravenously. Arterial blood pressure was monitored and recorded by using a femoral artery catheter and serum electrolytes, acid-base status and arterial hematocrit were determined immediately before the administration of thiopental. Thiopental was associated with a dose-related increase in mean arterial pressure of 32 +/- 11 mmHg (p < 0.0001). Thiopental also resulted in an increase in arterial pH of 0.08 +/- 0.03. A positive correlation between the magnitude of the pH change and the magnitude of the hypertensive response was suggested but did not reach statistical significance (p = 0.066). Of the other factors investigated, only serum-ionized calcium had a statistically significant association with the vascular response in that higher ionized calcium was associated with less hypertensive response (p = 0.014). The administration of thiopental to deeply hypothermic patients during cardiopulmonary bypass is associated with a dramatic increase in mean arterial blood pressure. The mechanism responsible for this vasoconstrictive response may involve thiopental's potentiation of the effects of norepinephrine in the peripheral vasculature.

Carbicarb, Sodium Bicarbonate, and Sodium Chloride in Hypoxic Lactic Acidosis: Effect on Arterial Blood Gases, Lactate Concentrations, Hemodynamic Variables, and Myocardial Intracellular pH

The effects of Carbicarb, sodium bicarbonate, and sodium chloride on arterial blood gases, lactate concentrations, hemodynamics, and myocardial intracellular pH were compared in hypoxic lactic acidosis with controlled carbon dioxide elimination. Twenty-one young mongrel dogs were anesthetized, mechanically ventilated, and randomly allocated into one of three treatment groups. After hypoxic lactic acidosis was induced and maintained, 2.5 mEq/kg of one of the agents was infused over 30 min. Arterial blood gases, pH, lactate concentrations, and hemodynamic variables were measured immediately prior to the infusion of the agent and 30 min after the infusion was completed. With sodium bicarbonate administration, there was a significant increase in arterial PCO2 as compared to both Carbicarb or sodium chloride administration. With Carbicarb administration, there was a significant increase in arterial pH, base excess, and cardiac index, without a significant increase in arterial lactate concentration as compared to sodium bicarbonate or sodium chloride administration. Stroke volume index was also increased significantly with decreased heart rate. The data suggest that Carbicarb administration in hypoxic lactic acidosis improved hemodynamics compared with sodium bicarbonate or sodium chloride administration. The increased stroke volume and cardiac contractility appear to be due to improved myocardial intracellular pH.

Seizures related to severe hypophosphataemia induced by mechanical ventilation

A patient with chronic obstructive pulmonary disease and acute respiratory failure developed grand mal seizures in the hours following onset of mechanical ventilation. These seizures were associated with an acute increase in arterial pH and were related to the occurrence of acute severe hypophosphataemia associated with recovery from respiratory acidosis.

Cerebral oxygen availability by NIR spectroscopy during transient hypoxia in humans

The effects of mild hypoxia on brain oxyhemoglobin, cytochrome a,a3 redox status, and cerebral blood volume were studied using near-infrared spectroscopy in eight healthy volunteers. Incremental hypoxia reaching 70% arterial O2 saturation was produced in normocapnia [end-tidal PCO2 (PETCO2) 36.9 +/- 2.6 to 34.9 +/- 3.4 Torr] or hypocapnia (PETCO2 32.8 +/- 0.6 to 23.7 +/- 0.6 Torr) by an 8-min rebreathing technique and regulation of inspired CO2. Normocapnic hypoxia was characterized by progressive reductions in arterial PO2 (PaO2, 89.1 +/- 3.5 to 34.1 +/- 0.1 Torr) with stable PETCO2, arterial PCO2 (PaCO2), and arterial pH and resulted in increases in heart rate (35%) systolic blood pressure (14%), and minute ventilation (5-fold). Hypocapnic hypoxia resulted in progressively decreasing PaO2 (100.2 +/- 3.6 to 28.9 +/- 0.1 Torr), with progressive reduction in PaCO2 (39.0 +/- 1.6 to 27.3 +/- 1.9 Torr), and an increase in arterial pH (7.41 +/- 0.02 to 7.53 +/- 0.03), heart rate (61%), and ventilation (3-fold). In the brain, hypoxia resulted in a steady decline of cerebral oxyhemoglobin content and a decrease in oxidized cytochrome a,a3. Significantly greater loss of oxidized cytochrome a,a3 occurred for a given decrease in oxyhemoglobin during hypocapnic hypoxia relative to normocapnic hypoxia. Total blood volume response during hypoxia also was significantly attenuated by hypocapnia, because the increase in volume was only half that of normocapnic subjects. We conclude that cytochrome a,a3 oxidation level in vivo decreases at mild levels of hypoxia. PaCO is an important determinant of brain oxygenation, because it modulates ventilatory, cardiovascular, and cerebral O2 delivery responses to hypoxia.

Continuous high volume venous-venous haemofiltration in acute renal failure.

Continuous, high volume, venous-venous haemofiltration was used as renal support in 28 critically ill patients with acute renal failure. Fifteen patients survived and were subsequently discharged from the ITU. Although haemofiltration was highly effective in reducing the blood urea and serum creatinine, only survivors demonstrated a significant increase in arterial pH (medians before and at two days 7.28 and 7.49 respectively, p less than 0.005) with a reduction in severity of their illness (median APACHE II scores before and at two days 23 and 16, p less than 0.005). Patients who died remained severely ill and acidotic (median APACHE II scores before and at two days 26 and 28; median arterial pH values 7.32 and 7.31 respectively) and by day two of treatment, marked differences between the patient groups in APACHE II scores, mean arterial pressure, arterial pH and urine flow rate had developed. Haemofiltration with the correction of acute uraemia alone does not necessarily lead to a reduction in the severity of illness which in the critically ill more frequently reflects other organ dysfunction.

Acute hypoxemia stimulates atrial natriuretic factor secretion in vivo.

The hypothesis was tested that acute hypoxemia may be a physiological stimulus for atrial natriuretic factor (ANF) secretion in anesthetized, spontaneously breathing rabbits. Base-line plasma ANF (range from 29.8 to 219 pg/ml; mean +/- SE = 87.0 +/- 14.1 pg/ml; n = 16 rabbits) was negatively correlated with base-line arterial PO2 (r = -0.759; P less than 0.01) but not with PCO2, pH, mean arterial blood pressure, central venous pressure (CVP), minute ventilation, heart rate, or type of anesthetics used. Acute hypoxemia (arterial PO2 22.3-44.3 mmHg) lasting 10 min increased plasma ANF levels over base line by 69.2 +/- 47.7 (SE) pg/ml at 6 min and 87.5 +/- 46.8 (SE) pg/ml at 9 min (P less than 0.01; n = 9). The increase in arterial pH and minute ventilation and the decrease of arterial PCO2 paralleled the changes in plasma ANF. Mean arterial blood pressure, CVP, and heart rate did not change significantly. ANF responses to hypoxemia (range from 4.4 to 423 pg/ml) correlated with base-line CVP (r = 0.761; P less than 0.01) and base-line ANF (r = 0.523; P less than 0.05) but with no other measured variable. Although the mediators of hypoxemia-induced release of ANF need to be explored further, this study raises the possibility that ANF might be involved in the adaptation to hypoxemia.

Role of endogenous opioids on ventilation and chemical control of breathing in pentobarbitone-anesthetized rats.

To investigate the role of endogenous opioids on ventilatory control in pentobarbitone-anesthetized rats, the opioid antagonists naloxone and naltrexone were studied for their effects on ventilation, arterial blood gases and on ventilatory responses to hypoxia and carbon dioxide. In animals breathing room air, intravenous administration of naloxone and naltrexone (4 and 10 mg/kg) caused a dose-related increase in tidal volume, respiratory rate and minute volume. These ventilatory responses were rapid in onset and were associated with a decrease in arterial PaCO2, an increase in arterial pH and an increase in arterial PaO2. Intravenous naloxone (4 mg/kg) antagonized the increase in PaCO2 and decrease in arterial pH induced by the administration of morphine (3 mg/kg, i.v.). In animals breathing 100% O2, intravenous administration of naloxone and naltrexone (4 and 10 mg/kg) did not stimulate ventilation. Furthermore, intracerebroventricular administration of naloxone (15 and 150 micrograms) had no measurable effect on ventilation. Ventilatory responses to both hypoxia and carbon dioxide were not augmented by intravenous naloxone (4 mg/kg) and naltrexone (4 and 10 mg/kg). In fact, the increase in respiratory rate due to hypoxia was significantly (p less than 0.05) reduced by naltrexone (10 mg/kg, i.v.). In conclusion, our results demonstrate that naloxone and naltrexone caused hyperventilation in pentobarbitone-anesthetized rats. This effect was probably triggered by stimulation of the peripheral arterial chemoreceptors and did not involve mechanisms directly associated with the central nervous system. However, endogenous opioids were not involved in the chemical control of breathing in pentobarbitone-anesthetized rats since ventilatory responses to hypoxia and carbon dioxide were not changed by administration of these opioid antagonists.

Red cell 2,3-diphosphoglycerate and hemoglobin--oxygen affinity during normal pregnancy.

The concentration of red cell 2,3-diphosphoglycerate (2,3-DPG), hemoglobin-oxygen affinity and other oxygen transport variables were determined during first, second and third trimester of normal pregnancy as well as 3 months post partum in 18 healthy women. The median concentration of red cell 2,3-DPG increased significantly from the first to the third trimester (16.1 to 17.0 mumol/gHb, p less than 0.01), whereas 2,3-DPG decreased significantly post partum (p less than 0.01). Normal pregnancy was also associated with relative anemia, a significant increase in arterial pH, hypocapnia and hypophosphatemia. The difference in hemoglobin concentration from the first trimester to 3 months post partum was correlated inversely with the difference in red cell 2,3-DPG content (r = -0.52, p less than 0.05). In spite of the variations in red cell 2,3-DPG, hemoglobin-oxygen affinity expressed as P50 at actual pH remained unchanged during pregnancy and post partum. The study suggests that the increased level of 2,3-DPG during pregnancy may in part represent compensation for physiologic anemia and also compensate for a factor leading to increased hemoglobin-oxygen affinity during pregnancy.

STIMULATION OF THE PERIPHERAL CHEMORECEPTORS WITH SODIUM BICARBONATE

The i.v. administration of sodium bicarbonate was found to cause an increase in arterial pH, followed by an increase in PaCO2. This caused a large increase in lung ventilation in in PaO2. Oxygen administration in human subjects, and anatomical denervation of the chemoreceptors in dogs, caused a substantial delay in the ventilatory responses to sodium bicarbonate. It was concluded that the i.v. administration of sodium bicarbonate provides a method of testing the presence of peripheral chemoreflexes which has the advantage of being independent of alveolar ventilation.

Mechanism of the serotonin effect on lung transvascular fluid and protein movement in awake sheep.

To see how serotonin affects filtration from lung vessels, we measured vascular pressures, lung lymph flow, lung lymph and blood plasma protein concentrations, arterial blood gases, cardiac output, and lung water content in unanesthetized sheep before and during intravenous serotonin infusions and compared serotonin effects with the effects of inflating a balloon in the left atrium in the same sheep. Serotonin caused a dose-related increase in lung lymph flow and a dose-related decrease in lymph-plasma protein concentration ratios. Steady-state 4-hour serotonin infusions at 4 mu-g/kg min-1 caused lymph flow to increase from 5.4 plus or minus 0.7 (SE) ml/hour to 8.3 plus or minus 1.3 ml/hour, lymph-plasma albumin ratios to fall from 0.78 plus or minus 0.05 to 0.72 plus or minus 0.04, lymph-plasma globulin ratios to fall from 0.64 plus or minus to 0.56 plus or minus 0.02, and pulmonary arterial and left atrial pressures to increase by 3 cm H-20 each. Lymph clearance and permeability-surface area products for eight protein fractions ranging from 36 A to 96 A in molecular radius during steady-state serotonin infusion studies were not significantly different from those during steady-state increased pressure studies. Four-hour infusions of serotonin at 4 mu-g/kg/kg min-1 caused a moderate fall in arterial Po-2 and a slight increase in arterial pH but did not affect cardiac output or cause pulmonary edema. We conclude that serotonin increases lung transvascular filtration primarily by increasing the transmural pressure gradient in exchanging vessels rather than by increasing vascular permeability.

Effects of changes in pO2, pCO2 and pH on the total vascular resistance of perfused cat kidneys.

1. The effects of change in arterial P(O2), P(CO2) and pH on the total vascular resistance (RVR) of the perfused cat kidney have been separately measured and expressed as +/- percentage deviations from control values.2. Control levels in arterial blood were pH 7.38, P(-) (O2) 160 mm Hg, in equilibrium with 5% CO(2).3. Increase in P(O2) alone, in excess of 220 mm Hg, raised RVR reversibly reading 108% control levels at a P(O2) 280 mm Hg (P = < 0.001).4. High levels of P(O2) favoured the onset of ;outflow block', which was characterized by irreversible increase in RVR accompanied by rise in plasma filtration fraction (F.F.) and in the extraction ratio for p-aminohippuric acid (PAH extraction).5. Reduction in P(O2) to 80 mm Hg decreased RVR by 4% (P = < 0.001).6. RVR was not significantly affected by pH changes within the range 7.25-7.45. Lowering arterial pH to 7.15 raised RVR by 4% (P = < 0.001) reversibly. Increase in arterial pH to 7.56 raised RVR by 6% (P = < 0.001) reversibly.7. Changes in arterial P(CO2) produced large inverse reversible changes in RVR. Halving P(CO2) raised RVR by 18%; doubling P(CO2) decreased RVR by 25%.8. Changes in RVR caused by alteration of arterial pH or P(CO2) were not accompanied by changes either in F.F. or in PAH extraction.

Effects of digitalis upon body electrolytes.

Studies of the electrolyte alterations in 54 dogs during 165 discrete digitalizations with acetyl strophantbidin to an endpoint of ventricular tachycardia are reported. In 94 per cent of digitalizatious, increase in arterial potassium concentration occurred. This was noted as early as five niinutes after drug administration. At the time of ventricular tachycardia, the increase was 0.67 mEq./L. When digitalization was carried to ventricular fibrillation, the increase was 3.1 mEq./L. In 75.5 per cent of the digitalizations, arterial sodium concentration decreased; average de crease was 2.6 mEq./L. At ventricular fibril lation, the decrease amounted to 11.0 mEq./L. Arterial calcium concentration and oxygen saturation were not altered. There was a modest decrease in CO 2 content and an increase in arterial pH and hcmatoerit. Peaking of the late portion of the T wave was common during acute digitalization and correlated with the increase in extracellular potassium concentration. The relationship of the electrolyte changes to the process of digitalization is discussed.

Effects of 2,4-Dinitrophenol on Respiration in the Dog

The intravenous administration of 2,4-dinitrophenol (DNP) to unanesthetized or anesthetized dogs produced an increase in arterial pH and decrease in arterial Pco2 which preceded any significant rise in body temperature. Thus the hyperventilation associated with DNP-administration appears not to be solely the result of increased production of CO2. Although DNP in small amounts stimulated respiration via the carotid body, larger doses still produced increased ventilation and pH and decreased Pco2 after denervation of the carotid bodies and bilateral vagotomy, thus demonstrating a stimulatory effect of DNP at some more central site as well. DNP increased the sensitivity of the respiratory center (or its afferent connections) to Pco2 and/or concentration of hydrogen ion. The similarities of respiratory effects of DNP and salicylate are discussed. An unexplained increase in ‘buffer base’ of the blood occurred in association with the respiratory alkalosis induced by DNP.