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Minimal volume ventilation in lung injury: With special reference to apnea and buffer treatment
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.ORCID iD: 0000-0003-0311-759X
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A fairly large portion of patients receiving surgical or intensive care will need mechanical ventilation at some point. The potential ventilator-induced lung injury (VILI) is thus of interest. One of the main causal factors in VILI is the cyclic energy shifts, i.e. tidal volumes, in the lung during mechanical ventilation. The problem can be approached in two ways. Firstly, one can utilize apneic oxygenation and thus not cause any tidal injuries at all. Secondly, and more traditionally, one can simply lower the tidal volumes and respiratory rates used. The following describes a series of animal experiments exploring these options.

In the first two papers, I explored and improved upon the methodology of apneic oxygenation. There is a generally held belief that it is only possible to perform apneic oxygenation by prior denitrogenation and by using 100% oxygen during the apnea. As 100% oxygen is toxic, this has prevented apneic oxygenation from more widespread use. The first paper proves that it is indeed possible to perform apneic oxygenation with less than 100% oxygen. I also calculated the alveolar nitrogen concentration which would conversely give the alveolar oxygen concentration. The second paper addresses the second large limitation of apneic oxygenation, i.e. hypercapnia. Using a high dose infusion of tris(hydroxymethyl)aminomethane (THAM) buffer, a pH > 7.2 could be maintained during apneic oxygenation for more than 4.5 hours.

In the last two papers, THAM’s properties as a proton acceptor are explored during respiratory acidosis caused by very low volume ventilation. In paper III, I found that THAM does not, in the long term, affect pH in respiratory acidosis after stopping the THAM infusion. It does, however, lower PVR, even though the PaCO2 of THAM-treated animals had rebounded to levels higher than that of the controls. In the last experiment, I used volumetric capnography to confirm our hypothesis that carbon dioxide elimination through the lungs was lower during the THAM infusion. Again, the PaCO2 rebounded after the THAM infusion had stopped and I concluded that renal elimination of protonated THAM was not sufficient.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. , 71 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1267
Keyword [en]
VILI, THAM, buffers, apneic oxygenation, respiratory acidosis, hypercapnia, low volume ventilation, mechanical ventilation, ultra-protective ventilation
National Category
Anesthesiology and Intensive Care
Research subject
Anaesthesiology and Intensive Care
Identifiers
URN: urn:nbn:se:uu:diva-305369ISBN: 978-91-554-9727-9OAI: oai:DiVA.org:uu-305369DiVA: diva2:1037505
Public defence
2016-12-02, Grönwallsalen, Ing 70, Akademiska Sjukhuset, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2016-11-10 Created: 2016-10-16 Last updated: 2016-11-16
List of papers
1. Non-toxic alveolar oxygen concentration without hypoxemia during apnoeic oxygenation: an experimental study
Open this publication in new window or tab >>Non-toxic alveolar oxygen concentration without hypoxemia during apnoeic oxygenation: an experimental study
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2011 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 55, no 9, 1078-1084 p.Article in journal (Refereed) Published
Abstract [en]

Background: Oxygenation without tidal breathing, i.e. apnoeic oxygenation in combination with extracorporeal carbon dioxide removal, might be an option in the treatment of acute respiratory failure. However, ventilation with 100% O(2), which is potentially toxic, is considered a prerequisite to ensure acceptable oxygenation. We hypothesized that trapping nitrogen (N(2)) in the lungs before the start of apnoeic oxygenation would keep the alveolar O(2) at a non-toxic level and still maintain normoxaemia. The aim was to test whether a predicted N(2) concentration would agree with a measured concentration at the end of an apnoeic period. Methods: Seven anaesthetized, muscle relaxed, endotracheally intubated pigs (22-27 kg) were ventilated in a randomized order with an inspired fraction of O(2) 0.6 and 0.8 at two positive end-expiratory pressure levels (5 cm and 10 cm H(2)O) before being connected to continuous positive airway pressure using 100% O(2) for apnoeic oxygenation. N(2) was measured before the start of and at the end of the 10-min apnoeic period. The predicted N(2) concentration was calculated from the initial N(2) concentration, the end-expiratory lung volume, and the anatomical dead space. Results: The mean difference and standard deviation between measured and predicted N(2) concentration was -0.5 +/- 2%, P = 0.587. No significant difference in the agreement between measured and predicted N(2) concentrations was seen in the four settings. Conclusions: This study indicates that it is possible to predict and keep alveolar N(2) concentration at a desired level and, thus, alveolar O(2) concentration at a non-toxic level during apnoeic oxygenation.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-160124 (URN)10.1111/j.1399-6576.2011.02499.x (DOI)000295102500006 ()
Available from: 2011-10-17 Created: 2011-10-17 Last updated: 2016-10-16Bibliographically approved
2. Intensive buffering can keep pH above 7.2 for over 4 h during apnea: an experimental porcine study
Open this publication in new window or tab >>Intensive buffering can keep pH above 7.2 for over 4 h during apnea: an experimental porcine study
2013 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 57, no 1, 63-70 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

Ventilation with low tidal volumes reduces mortality in acute respiratory distress syndrome. A further reduction of tidal volumes might be beneficial, and it is known that apneic oxygenation (no tidal volumes) with arteriovenous CO(2) removal can keep acid-base balance and oxygenation normal for at least 7 h in an acute lung injury model. We hypothesized that adequate buffering might be another approach and tested whether tris-hydroxymethyl aminomethane (THAM) alone could keep pH at a physiological level during apneic oxygenation for 4 h.

METHODS:

Six pigs were anesthetized, muscle relaxed, and normoventilated. The lungs were recruited, and apneic oxygenation as well as administration of THAM, 20 mmol/kg/h, was initiated. The experiment ended after 270 min, except one that was studied for 6 h.

RESULTS:

Two animals died before the end of the experiment. Arterial pH and arterial carbon dioxide tension (PaCO(2) ) changed from 7.5 (7.5, 7.5) to 7.3 (7.2, 7.3) kPa, P < 0.001 at 270 min, and from 4.5 (4.3, 4.7) to 25 (22, 28) kPa, P < 0.001, respectively. Base excess increased from 5 (3, 6) to 54 (51, 57) mM, P < 0.001. Cardiac output and arterial pressure were well maintained. The pig, which was studied for 6 h, had pH 7.27 and PaCO(2) 27 kPa at that time.

CONCLUSION:

With intensive buffering using THAM, pH can be kept in a physiologically acceptable range for 4 h during apnea.

National Category
Medical and Health Sciences
Research subject
Clinical Physiology
Identifiers
urn:nbn:se:uu:diva-188729 (URN)10.1111/aas.12012 (DOI)000312271800009 ()23167283 (PubMedID)
Available from: 2012-12-19 Created: 2012-12-19 Last updated: 2016-10-16Bibliographically approved
3. THAM reduces CO2-associated increase in pulmonary vascular resistance: an experimental study in lung-injured piglets
Open this publication in new window or tab >>THAM reduces CO2-associated increase in pulmonary vascular resistance: an experimental study in lung-injured piglets
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2015 (English)In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, no 1, 331Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Low tidal volume (VT) ventilation is recommended in patients with acute respiratory distress syndrome (ARDS). This may increase arterial carbon dioxide tension (PaCO2), decrease pH, and augment pulmonary vascular resistance (PVR). We hypothesized that Tris(hydroxymethyl)aminomethane (THAM), a pure proton acceptor, would dampen these effects, preventing the increase in PVR.

METHODS: A one-hit injury ARDS model was established by repeated lung lavages in 18 piglets. After ventilation with VT of 6 ml/kg to maintain normocapnia, VT was reduced to 3 ml/kg to induce hypercapnia. Six animals received THAM for 1 h, six for 3 h, and six serving as controls received no THAM. In all, the experiment continued for 6 h. The THAM dosage was calculated to normalize pH and exhibit a lasting effect. Gas exchange, pulmonary, and systemic hemodynamics were tracked. Inflammatory markers were obtained at the end of the experiment.

RESULTS: In the controls, the decrease in VT from 6 to 3 ml/kg increased PaCO2 from 6.0±0.5 to 13.8±1.5 kPa and lowered pH from 7.40±0.01 to 7.12±0.06, whereas base excess (BE) remained stable at 2.7±2.3 mEq/L to 3.4±3.2 mEq/L. In the THAM groups, PaCO2 decreased and pH increased above 7.4 during the infusions. After discontinuing the infusions, PaCO2 increased above the corresponding level of the controls (15.2±1.7 kPa and 22.6±3.3 kPa for 1-h and 3-h THAM infusions, respectively). Despite a marked increase in BE (13.8±3.5 and 31.2±2.2 for 1-h and 3-h THAM infusions, respectively), pH became similar to the corresponding levels of the controls. PVR was lower in the THAM groups (at 6 h, 329±77 dyn∙s/m(5) and 255±43 dyn∙s/m(5) in the 1-h and 3-h groups, respectively, compared with 450±141 dyn∙s/m(5) in the controls), as were pulmonary arterial pressures.

CONCLUSIONS: The pH in the THAM groups was similar to pH in the controls at 6 h, despite a marked increase in BE. This was due to an increase in PaCO2 after stopping the THAM infusion, possibly by intracellular release of CO2. Pulmonary arterial pressure and PVR were lower in the THAM-treated animals, indicating that THAM may be an option to reduce PVR in acute hypercapnia.

National Category
Anesthesiology and Intensive Care
Research subject
Anaesthesiology and Intensive Care; Physiology
Identifiers
urn:nbn:se:uu:diva-264209 (URN)10.1186/s13054-015-1040-4 (DOI)000361433900001 ()26376722 (PubMedID)
Funder
Swedish Research Council, K2015-99X-22731-01-4Swedish Heart Lung Foundation
Available from: 2015-10-07 Created: 2015-10-07 Last updated: 2016-10-16Bibliographically approved
4. THAM administration reduces pulmonary carbon dioxide elimination, causing rebound in arterial carbon dioxide tension: An experimental study in hypoventilated pigs
Open this publication in new window or tab >>THAM administration reduces pulmonary carbon dioxide elimination, causing rebound in arterial carbon dioxide tension: An experimental study in hypoventilated pigs
(English)Manuscript (preprint) (Other academic)
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-304710 (URN)
Available from: 2016-10-08 Created: 2016-10-07 Last updated: 2016-10-16

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