Martin O. Krebs

Renal nerves are not involved in sodium and water retention during mechanical ventilation in awake dogs

Background The role of renal nerves during positive end‐expiratory pressure ventilation (PEEP) has only been investigated in surgically stressed, anesthetized, unilaterally denervated dogs. Anesthesia, sedation, and surgical stress, however, decrease urine volume and sodium excretion and increase renal sympathetic nerve activity independent of PEEP. This study investigated in awake dogs the participation of renal nerves in mediating volume and water retention during PEEP. Methods Eight tracheotomized, trained, awake dogs were used. The protocol consisted of 60 min of spontaneous breathing at a continuous positive airway pressure of 4 cm H2 O, followed by 120 min of controlled mechanical ventilation with a mean PEEP of 15‐17 cm H2 O (PEEP), and 60 min of continuous positive airway pressure. Two protocols were performed on intact dogs, in which volume expansion had (hypervolemic; electrolyte solution, 0.5 ml [middle dot] kg‐1 [middle dot] min‐1) and had not (normovolemic) been instituted. This was repeated on the same dogs 2 or 3 weeks after bilateral renal denervation. Results Hypervolemic dogs excreted more sodium and water than did normovolemic dogs. There was no difference between intact and renal‐denervated dogs. Arterial pressure did not decrease when continuous positive airway pressure was switched to PEEP. Plasma renin activity, aldosterone, and antidiuretic hormone concentrations were greater in normovolemic dogs. The PEEP increased aldosterone and antidiuretic hormone concentrations only in normovolemic dogs. Conclusions In conscious dogs, renal nerves have no appreciable contribution to sodium and water retention during PEEP. Retention in normovolemic dogs seems to be primarily caused by an activation of the renin‐angiotensin system and an increase in the antidiuretic hormone. Excretion rates depended on the volume status of the dogs.

Methohexital Impairs Osmoregulation: Studies in Conscious and Anesthetized Volume-expanded Dogs

Background Anesthetic agents influence central regulations. This study investigated the effects of methohexital anesthesia on renal and hormonal responses to acute sodium and water loading in dogs in the absence of surgical stress. Methods Fourteen experiments (two in each dog) were performed in seven well-trained, chronically tracheotomized beagle dogs kept in highly standardized environmental and dietary conditions (2.5 mmol sodium and 91 ml water/kg body weight daily). Experiments lasted 3 h, while the dogs were conscious (7 experiments) or, after 1 h control, while they were anesthetized (7 experiments) with methohexital (initial dose 6.6 mg/kg body weight and maintenance infusion 0.34 mg *symbol* min sup -1 *symbol* kg sup -1 body weight) over a period of 2 h. In both experiments, extracellular volume expansion was performed by intravenous infusion of a balanced isoosmolar electrolyte solution (0.5 ml *symbol* min sup -1 *symbol* kg sup -1 body weight). Normal arterial blood gases were maintained by controlled mechanical ventilation. In another five dogs the same protocol was used, and vasopressin (0.05 mU *symbol* min sup -1 *symbol* kg sup -1 body weight) was infused intravenously during methohexital anesthesia. Results Values are given as means. During methohexital anesthesia, mean arterial pressure decreased from 108 to 101 mmHg, and heart rate increased from 95 to 146 beats/min. Renal sodium excretion decreased; urine volume increased; and urine osmolarity decreased from 233 to 155 mosm/l, whereas plasma osmolarity increased from 301 to 312 mosm/l because of an increase in plasma sodium concentration from 148 to 154 mmol/l. Plasma renin activity, plasma aldosterone concentration, plasma atrial natriuretic peptide, and plasma antidiuretic hormone concentrations (range 1.8-2.8 pg/ml) did not change in either protocol. In the presence of exogenous vasopressin (antidiuretic hormone 3.3 pg/ml), water diuresis did not occur, and neither plasma osmolarity nor the plasma concentration of sodium changed. Conclusions Methohexital may impair osmoregulation by inhibiting adequate pituitary antidiuretic hormone release in response to an osmotic challenge.

Renal and hemodynamic effects of losartan in conscious dogs during controlled mechanical ventilation

In 12 conscious dogs, we investigated whether the angiotensin II-receptor antagonist losartan increases renal sodium excretion and urine volume during controlled mechanical ventilation (CMV) with positive end-expiratory pressure. In four experimental protocols, the dogs were extracellular volume (ECV) expanded (electrolyte solution, 0.5 ml. kg-1. min-1 iv) or not and received losartan (100 micrograms. kg-1. min-1 iv) or not. They breathed spontaneously during the 1st and 4th hour and received CMV with positive end-expiratory pressure (mean airway pressure 20 cmH2O) during the 2nd and 3rd hours. In the expansion group, dogs with losartan excreted approximately 18% more sodium (69 +/- 7 vs. 38 +/- 5 micromol. min-1. kg-1) and 15% more urine during the 2 h of CMV because of a higher glomerular filtration rate (5.3 +/- 0.3 vs. 4.5 +/- 0.2 ml. min-1. kg-1) and the tubular effects of losartan. In the group without expansion, sodium excretion (2.0 +/- 0.6 vs. 2.6 +/- 1.0 micromol. min-1. kg-1) and glomerular filtration rate (3.8 +/- 0.3 vs. 3.8 +/- 0.4 ml. min-1. kg-1) did not change, and urine volume decreased similarly in both groups during CMV. Plasma vasopressin and aldosterone increased in both groups, and plasma renin activity increased from 4.9 +/- 0.7 to 7.8 +/- 1.3 ng ANG I. ml-1. h-1 during CMV in nonexpanded dogs without losartan. Mean arterial pressure decreased by 10 mmHg in nonexpanded dogs with losartan. In conclusion, losartan increases sodium excretion and urine volume during CMV if the ECV is expanded. If the ECV is not expanded, a decrease in mean arterial blood pressure and/or an increase in aldosterone and vasopressin during CMV attenuates the renal effects of losartan.In 12 conscious dogs, we investigated whether the angiotensin II-receptor antagonist losartan increases renal sodium excretion and urine volume during controlled mechanical ventilation (CMV) with positive end-expiratory pressure. In four experimental protocols, the dogs were extracellular volume (ECV) expanded (electrolyte solution, 0.5 ml ⋅ kg-1 ⋅ min-1iv) or not and received losartan (100 μg ⋅ kg-1 ⋅ min-1iv) or not. They breathed spontaneously during the 1st and 4th hour and received CMV with positive end-expiratory pressure (mean airway pressure 20 cmH2O) during the 2nd and 3rd hours. In the expansion group, dogs with losartan excreted ∼18% more sodium (69 ± 7 vs. 38 ± 5 μmol ⋅ min-1 ⋅ kg-1) and 15% more urine during the 2 h of CMV because of a higher glomerular filtration rate (5.3 ± 0.3 vs. 4.5 ± 0.2 ml ⋅ min-1 ⋅ kg-1) and the tubular effects of losartan. In the group without expansion, sodium excretion (2.0 ± 0.6 vs. 2.6 ± 1.0 μmol ⋅ min-1 ⋅ kg-1) and glomerular filtration rate (3.8 ± 0.3 vs. 3.8 ± 0.4 ml ⋅ min-1 ⋅ kg-1) did not change, and urine volume decreased similarly in both groups during CMV. Plasma vasopressin and aldosterone increased in both groups, and plasma renin activity increased from 4.9 ± 0.7 to 7.8 ± 1.3 ng ANG I ⋅ ml-1 ⋅ h-1during CMV in nonexpanded dogs without losartan. Mean arterial pressure decreased by 10 mmHg in nonexpanded dogs with losartan. In conclusion, losartan increases sodium excretion and urine volume during CMV if the ECV is expanded. If the ECV is not expanded, a decrease in mean arterial blood pressure and/or an increase in aldosterone and vasopressin during CMV attenuates the renal effects of losartan.

The kidney: a target organ during mechanical ventilation

Mechanical ventilation increases airway pressure during inspiration and, in addition with the application of positive end-expiratory pressure (PEEP), also during expiration. The resulting increase of intrathoracic (interpleural) pressure impairs venous return and may decrease cardiac output and mean arterial pressure. The — albeit small — simultaneous increase of intraabdominal pressure also impairs venous return and leads to an increase of renal venous pressure, which affects the renal excretory function. Reversal of the physiological interplay between abdominal and thoracic driving forces into a highly unphysiological situation, produces a variety of physical, hormonal, and neural changes which, in turn, act on the kidney as a target organ. Renal function itself may not be impaired, however, the kidneys respond to these various stimuli by decreasing sodium and water excretion. Sodium and water retention decrease peripheral and pulmonary diffusion of oxygen and carbon dioxide. Due to enlargement of the interstitial space, the exchange of substrates is impaired. Thus, the benefits of mechanical ventilation may partially be diminished by these undesired side effects. In 1980, it was demonstrated in ICU patients, in whom daily sodium and water balances were checked over a period of several consecutive days, how effectively electrolyte and fluid balance can be normalized by decreasing airway pressure [l].