Non Carbonic Buffer Power of Critical Ill Patients With Sepsis

Changes in Acid-base Variables Induced by Acute Variations in Partial Pressure of Carbon Dioxide in Whole Blood and Isolated Plasma of Septic Critically Ill Patients and Healthy Volunteers: an In-vitro Study

Alterations of acid-base equilibrium are very common in critically ill patients and understanding their pathophysiology can be important to improve clinical treatment.

The human organism is protected against acid-base disorders by several compensatory mechanisms that minimize pH variations in case of blood variations in carbon dioxide content. The aim of the present study is to quantify the buffer power, i.e. the capacity to limit pH variations in response to carbon dioxide changes, in critically ill septic patients and compare these results with data collected from healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Acid-Base Imbalance; Respiratory Acidosis; Respiratory Alkalosis
• Intervention / Treatment: Diagnostic test: In vitro determination of non-carbonic buffer power; Diagnostic test: Classic description of acid-base status

Detailed Description

Alterations of acid-base equilibrium are very common in critically ill patients and understanding their pathophysiology can be important to improve clinical treatment.

The human body is protected against acid-base disorders by several compensatory mechanisms that minimize pH variations in response to acid-base derangements.

The present study focuses on the acute compensatory mechanisms of respiratory acid-base derangements, i.e., respiratory acidosis and respiratory alkalosis. In this case the non-carbonic buffers are constituted by albumin and phosphates in plasma, with the addition of hemoglobin in whole blood.

Aim of the present in-vitro study is to measure the buffer power of non-carbonic weak acids contained in whole blood and isolated plasma, assess the relative contribution of red blood cells and plasma proteins and perform a comparison between septic patients and healthy controls.

• Study Type: Observational
• Enrollment (Actual): 36

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20122
    • IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with sepsis or septic shock admitted to the ICU will be enrolled. Furthermore, healthy volunteers recruited from ICU staff members and relatives will be enrolled as control group.

Description

Inclusion Criteria:

• Septic patients and healthy volunteers

Exclusion Criteria:

• age < 18 years and pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Septic patients; Patients with sepsis or septic shock according to the SEPSIS-III (Singer M Jama 2016) admitted to the general Intensive Care Unit	Diagnostic test: In vitro determination of non-carbonic buffer power; In vitro measurement of the non-carbonic buffer power by the means of equilibration of whole blood and isolated plasma with gas mixtures containing different concentrations of carbon dioxide; Diagnostic test: Classic description of acid-base status; Measurement of plasma electrolytes, hemoglobin concentration, albumin and phosphates to compute acid-base variables according to Stewart's approach.
Healthy volunteers; Subjects without known respiratory, cardiovascular, hepatic, renal or hematologic diseases.	Diagnostic test: In vitro determination of non-carbonic buffer power; In vitro measurement of the non-carbonic buffer power by the means of equilibration of whole blood and isolated plasma with gas mixtures containing different concentrations of carbon dioxide; Diagnostic test: Classic description of acid-base status; Measurement of plasma electrolytes, hemoglobin concentration, albumin and phosphates to compute acid-base variables according to Stewart's approach.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-carbonic buffer power	Non-carbonic buffer power (beta) of whole blood and isolated plasma [expressed as variations in bicarbonate concentration divided by variations in pH).	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Strong Ion Difference variations induced by carbon dioxide	Variations in Strong Ion Difference of whole blood and plasma [expressed in milliequivalents per Liter], induced by acute in vitro changes of carbon dioxide	1 day
Bicarbonate Variations induced by carbon dioxide	Variations in bicarbonate concentration of whole blood and plasma [expressed in milliequivalents per Liter], induced by acute in vitro changes of carbon dioxide	1 day
Oxidized albumin	Oxidized albumin [expressed as percentage of total albumin concentration]	1 day
Correlation between hematocrit values and Strong Ion Difference variations	Correlation between hematocrit [expressed as percentage] values and Strong Ion Difference variations [expressed in mEq/L] induced by acute in vitro changes of Carbon Dioxide. Acute variations in partial pressure of carbon dioxide cause changes in Strong Ion Difference. The hypothesis is that the magnitude of Strong Ion Difference variations correlate to the hematocrit, being the red blood cell the major source of electrolytes. The higher the hematocrit, the higher the possible change in Strong Ion Difference induced by acute variations in partial pressure of carbon dioxide.	1 day

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
• Investigators: Principal Investigator: Thomas Langer, MD, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano; Study Director: Antonio Pesenti, MD, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano; Study Chair: Giacomo Grasselli, MD, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2018
• Primary Completion (Actual): February 20, 2019
• Study Completion (Actual): February 20, 2019

Study Registration Dates

• First Submitted: April 9, 2018
• First Submitted That Met QC Criteria: April 18, 2018
• First Posted (Actual): April 19, 2018

Study Record Updates

• Last Update Posted (Actual): April 25, 2019
• Last Update Submitted That Met QC Criteria: April 24, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Acid-base equilibrium; Stewart's approach; In vitro study; Respiratory acid-base derangements
• Additional Relevant MeSH Terms: Metabolic Diseases; Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency; Hyperventilation; Alkalosis; Acidosis; Acid-Base Imbalance; Alkalosis, Respiratory; Acidosis, Respiratory
• Other Study ID Numbers: Buffer power

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No