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Cardiopulmonary Resuscitation: Pharmacological Interventions for Augmentation of Cerebral Blood Flow
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cardiac arrest results in immediate interruption of blood flow. The primary goal of cardiopulmonary resuscitation (CPR) is to re-establish blood flow and hence oxygen delivery to the vital organs. This thesis describes different pharmacological interventions aimed at increasing cerebral blood flow during CPR and after restoration of spontaneous circulation (ROSC).

In a porcine model of cardiac arrest, continuous infusion of adrenaline generated higher cortical cerebral blood flow during CPR as compared to bolus administration of adrenaline. While bolus doses resulted in temporary peaks in cerebral blood flow, continuous infusion led to a sustained increase in this flow.

Administration of vasopressin resulted in higher cortical cerebral blood flow and a lower cerebral oxygen extraction ratio as compared to continuous infusion of adrenaline during CPR. In addition, vasopressin generated higher coronary perfusion pressure during CPR and increased the likelihood of achieving ROSC.

Parameters of coagulation and inflammation were measured after successful resuscitation from cardiac arrest. Immediately after ROSC, thrombin-antithrombin complex, a marker of thrombin generation, was elevated and eicosanoid levels were increased, indicating activation of coagulation and inflammation after ROSC. The thrombin generation was accompanied by a reduction in antithrombin. In addition, there was substantial haemoconcentration in the initial period after ROSC.

By administration of antithrombin during CPR, supraphysiological levels of antithrombin were achieved. However, antithrombin administration did not increase cerebral circulation or reduce reperfusion injury, as measured by cortical cerebral blood flow, cerebral oxygen extraction and levels of eicosanoids, after ROSC.

In a clinical study, the adrenaline dose interval was found to be longer than recommended in the majority of cases of cardiac arrest. Thus, the adherence to recommended guidelines regarding the adrenaline dose interval seems to be poor.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2004. , p. 59
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1355
Keyword [en]
Anaesthesiology and intensive care, Adrenaline (epinephrine), Cardiac arrest, Cardiopulmonary resuscitation, Cerebral blood flow, Guidelines, Post-resuscitation period, Vasopressin
Keyword [sv]
Anestesiologi och intensivvård
National Category
Anesthesiology and Intensive Care
Identifiers
URN: urn:nbn:se:uu:diva-4281ISBN: 91-554-5981-1 (print)OAI: oai:DiVA.org:uu-4281DiVA, id: diva2:164689
Public defence
2004-06-02, Hedstrandsalen, Akademiska Sjukhuset ing. 70, Uppsala, 09:15
Opponent
Supervisors
Available from: 2004-05-07 Created: 2004-05-07Bibliographically approved
List of papers
1. Increased cortical cerebral blood flow by continuous infusion of epinephrine during experimental cardiopulmonary resuscitation
Open this publication in new window or tab >>Increased cortical cerebral blood flow by continuous infusion of epinephrine during experimental cardiopulmonary resuscitation
2003 (English)In: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 57, no 3, p. 299-307Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To study the effects of continuously administered adrenaline (epinephrine), compared to bolus doses, on the dynamics of cortical cerebral blood flow during experimental cardiopulmonary resuscitation (CPR), and after restoration of spontaneous circulation (ROSC).

METHODS: Ventricular fibrillation was induced in 24 anaesthetised pigs. After a 5-min non-intervention interval, closed-chest CPR was started. The animals were randomised into two groups. One group received three boluses of adrenaline (20 microg/kg) at 3-min intervals. The other group received an initial bolus of adrenaline (20 microg/kg) followed by an infusion of adrenaline (10 microg/kg x min). After 9 min of CPR, defibrillation was attempted, and if spontaneous circulation was achieved the adrenaline infusion was stopped. Cortical cerebral blood flow was measured continuously using Laser-Doppler flowmetry. Jugular bulb oxygen saturation was measured to reflect global cerebral oxygenation. Repeated measurements of 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) in jugular bulb plasma were performed to evaluate cerebral oxidative injury.

RESULTS: During CPR mean cortical cerebral blood flow was significantly higher (P=0.009) with a continuous adrenaline infusion than with repeated bolus doses. Following ROSC there was no significant difference in cortical cerebral blood flow between the two study groups. No differences in coronary perfusion pressure, rate of ROSC, jugular bulb oxygen saturation or 8-iso-PGF(2alpha) were seen between the study groups.

CONCLUSIONS: Continuous infusion of adrenaline (10 microg/kg x min) generated a more sustained increase in cortical cerebral blood flow during CPR as compared to intermittent bolus doses (20 microg/kg every third minute). Thus, continuous infusion might be a more appropriate way to administer adrenaline as compared to bolus doses during CPR.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-91827 (URN)10.1016/S0300-9572(03)00031-5 (DOI)12804807 (PubMedID)
Available from: 2004-05-07 Created: 2004-05-07 Last updated: 2017-12-14Bibliographically approved
2. Vasopressin versus continuous adrenaline during experimental cardiopulmonary resuscitation
Open this publication in new window or tab >>Vasopressin versus continuous adrenaline during experimental cardiopulmonary resuscitation
2004 (English)In: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 62, no 1, p. 61-69Article in journal (Refereed) Published
Abstract [en]

Objective: To evaluate the effects of a bolus dose of vasopressin compared to continuous adrenaline (epinephrine) infusion on vital organ blood flow during cardiopulmonary resuscitation (CPR). Methods: Ventricular fibrillation was induced in 24 anaesthetised pigs. After a 5-min non-intervention interval, CPR was started. After 2 min of CPR the animals were randomly assigned to receive either vasopressin (0.4 U/kg) or adrenaline (bolus of 20 μg/kg followed by continuous infusion of 10 μg/(kg min)). Defibrillation was attempted after 9 min of CPR. Results: Vasopressin generated higher cortical cerebral blood flow (P<0.001) and lower cerebral oxygen extraction (P<0.001) during CPR compared to continuous adrenaline. Coronary perfusion pressure during CPR was higher in vasopressin-treated pigs (P<0.001) and successful resuscitation was achieved in 12/12 in the vasopressin group versus 5/12 in the adrenaline group (P=0.005). Conclusions: In this experimental model, vasopressin caused a greater increase in cortical cerebral blood flow and lower cerebral oxygen extraction during CPR compared to continuous adrenaline. Furthermore, vasopressin generated higher coronary perfusion pressure and increased the likelihood of restoring spontaneous circulation.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-91828 (URN)10.1016/j.resuscitation.2004.01.034 (DOI)15246585 (PubMedID)
Available from: 2004-05-07 Created: 2004-05-07 Last updated: 2017-12-14Bibliographically approved
3. Adrenaline administration during cardiopulmonary resuscitation: poor adherence to clinical guidelines
Open this publication in new window or tab >>Adrenaline administration during cardiopulmonary resuscitation: poor adherence to clinical guidelines
Show others...
2004 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 48, no 7, p. 909-913Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Adrenaline does not appear to improve the outcome after cardiac arrest in clinical trials in spite of beneficial effects in experimental studies. The objective of this study was to determine whether adrenaline was administered in accordance with advanced cardiac life support (ACLS) guidelines during adult cardiopulmonary resuscitation (CPR). METHODS: From 15 January to 31 December 2000, all patients at Uppsala University Hospital in whom CPR was attempted were registered prospectively. The duration of CPR was documented in the register and the total dose of adrenaline was retrieved retrospectively from patient records. From these data the average interval between adrenaline doses was calculated. RESULTS: Data for evaluation of the between-dose interval of adrenaline was available in 53 of 107 registered cardiac arrests. In 68% (36/53) the average between-dose interval was longer than the 3-5 min recommended in the guidelines, and 8% (4/53) received no adrenaline. The median interval between adrenaline doses during CPR was 6.5 min (25th-75th percentile: 5.1-10.4). Adherence to guidelines was lower in out-of-hospital cardiac arrest than in in-hospital cardiac arrest (P = 0.01). CONCLUSIONS: In the majority of cases adrenaline did not appear to be administered according to current ACLS guidelines.

Keyword
Adult, Aged, Aged; 80 and over, Cardiopulmonary Resuscitation, Epinephrine/*administration & dosage, Female, Humans, Male, Middle Aged, Practice Guidelines, Time Factors
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-91829 (URN)10.1111/j.1399-6576.2004.00440.x (DOI)15242439 (PubMedID)
Available from: 2004-05-07 Created: 2004-05-07 Last updated: 2017-12-14Bibliographically approved
4. Antithrombin reduction after experimental cardiopulmonary resuscitation
Open this publication in new window or tab >>Antithrombin reduction after experimental cardiopulmonary resuscitation
2003 (English)In: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 59, no 2, p. 229-236Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To determine whether activation of coagulation and inflammation during cardiac arrest results in a reduction of antithrombin (AT) and an increase in thrombin-antithrombin (TAT) complex during reperfusion.

METHODS: Ventricular fibrillation (VF) was induced in ten anaesthetized pigs. After a 5-min non-intervention interval, closed-chest cardiopulmonary resuscitation (CPR) was performed for 9 min before defibrillation was attempted. If restoration of spontaneous circulation (ROSC) was achieved, the animals were observed for 4 h and repeated blood samples were taken for assay of AT, TAT and eicosanoids (8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha)).

RESULTS: AT began to decrease 15 min after ROSC and the reduction continued throughout the observation period (P<0.05). The lowest mean value (79%) occurred 60 min after ROSC. The TAT level was increased during the first 3 h after ROSC (P<0.05), indicating thrombin generation. The eicosanoids were increased throughout the observation period (P<0.05).

CONCLUSIONS: AT is reduced and TAT and eicosanoids are increased after cardiac arrest, indicating activation of coagulation and inflammation.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-91830 (URN)10.1016/S0300-9572(03)00182-5 (DOI)14625115 (PubMedID)
Available from: 2004-05-07 Created: 2004-05-07 Last updated: 2017-12-14Bibliographically approved
5. Antithrombin administration during experimental cardiopulmonary resuscitation
Open this publication in new window or tab >>Antithrombin administration during experimental cardiopulmonary resuscitation
2004 (English)In: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 62, no 1, p. 71-78Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To determine whether antithrombin (AT) administration during cardiopulmonary resuscitation (CPR) increased cerebral circulation and reduced reperfusion injury.

METHODS: Ventricular fibrillation was induced in 24 anaesthetised pigs. After a 5-min non-intervention interval, CPR was started. The animals were randomised into two groups. The treatment group received AT (250 U/kg) and the control group received placebo, after 7 min of CPR. Defibrillation was attempted after 9 min of CPR. If restoration of spontaneous circulation (ROSC) was achieved, the animals were observed for 4 h. Cortical cerebral blood flow was measured using laser-Doppler flowmetry. Cerebral oxygen extraction was calculated to reflect the relation between global cerebral circulation and oxygen demand. Measurements of eicosanoids (8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha)), AT, thrombin-antithrombin complex (TAT) and soluble fibrin in jugular bulb plasma were performed to detect any signs of cerebral oxidative injury, inflammation and coagulation.

RESULTS: There was no difference between the groups in cortical cerebral blood flow, cerebral oxygen extraction, or levels of eicosanoids, TAT or soluble fibrin in jugular bulb plasma after ROSC. In the control group reduction of AT began 15 min after ROSC and continued throughout the entire observation period (P < 0.05). Eicosanoids and TAT were increased compared to baseline in all animals (P < 0.01).

CONCLUSIONS: In this experimental model of CPR, AT administration did not increase cerebral circulation or reduce reperfusion injury after ROSC.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-91831 (URN)10.1016/j.resuscitation.2004.02.010 (DOI)15246586 (PubMedID)
Available from: 2004-05-07 Created: 2004-05-07 Last updated: 2017-12-14Bibliographically approved

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