Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest

Eastwood, Glenn M; Nichol, Alistair; Hodgson, Carol; Parke, Rachael; McGuinness, Shay; Nielsen, Niklas; Bernard, Stephen; Skrifvars, Markus B.; Taccone, Fabio Silvio; Archer, John S.; Kutsogiannis, Demetrios J.; Dankiewicz, Josef; Lilja, Gisela; Cronberg, Tobias; Kirkegaard, Hans; Capellier, Gilles; Landoni, Giovanni; Horn, Janneke; Olasveengen, Theresa M.; Arabi, Yaseen M.; Chia, Yew Woon; Markota, Andrej; Hænggi, Matthias; Wise, Matt P.; Grejs, Anders Morten; Christensen, Steffen; Munk-Andersen, Heidi; Granfeldt, Asger; Andersen, Geir Øystein; Qvigstad, Eirik; Flaa, Arnljot; Thomas, Matthew; Sweet, Katie; Bewley, Jeremy; Bäcklund, Minna; Tiainen, Marjaana; Iten, Manuela; Levis, Anja; Peck, Leah; Walsham, James; Deane, Adam M; Ghosh, Angaj; Annoni, Filippo; Chen, Yan; Knight, David; Lesona, Eden; Tlayjeh, Haytham; Svenšek, Franc; McGuigan, Peter; Cole, Jade; Pogson, David; Hilty, Matthias P.; Düring, Joachim; Bailey, Michael; Paul, Eldho; Ady, Bridget; Ainscough, Kate; Hunt, Anna; Monahan, Sarah; Trapani, Tony; Fahey, Ciara; Bellomo, Rinaldo

doi:10.1056/nejmoa2214552

Cited by 65 publications

(12 citation statements)

References 38 publications

(55 reference statements)

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“…The development of non-invasive techniques to identify patient-specific pathophysiology is an essential avenue for future research. An impairment of oxygen diffusion may explain why not all HIBI patients benefit from augmented convective CDO 2 [ 7 , 8 , 14 , 55 , 76 ]. Studies to date have only targeted convective CDO 2 or implemented singular interventions [ 7 – 14 , 56 ].…”

Section: Discussionmentioning

confidence: 99%

“…Clinically, impaired CO 2 reactivity may limit the ability of hypercapnia to improve convective CDO 2 . This may help explain why initial small clinical trials [ 10 , 11 ] and the recently published TAME trial [ 55 ] did not demonstrate differences in neurologic outcome in HIBI patients with mild hypercapnia versus normocapnia. TAME randomised 1700 out-of-hospital cardiac arrest patients to mild hypercapnia (PaCO 2 50–55 mmHg) vs normocapnia (PaCO 2 35–45 mmHg) for 24 h post-ROSC.…”

Section: Stage 1: Convective Oxygen Deliverymentioning

confidence: 99%

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Clinical targeting of the cerebral oxygen cascade to improve brain oxygenation in patients with hypoxic–ischaemic brain injury after cardiac arrest

et al. 2023

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The cerebral oxygen cascade includes three key stages: (a) convective oxygen delivery representing the bulk flow of oxygen to the cerebral vascular bed; (b) diffusion of oxygen from the blood into brain tissue; and (c) cellular utilisation of oxygen for aerobic metabolism. All three stages may become dysfunctional after resuscitation from cardiac arrest and contribute to hypoxic–ischaemic brain injury (HIBI). Improving convective cerebral oxygen delivery by optimising cerebral blood flow has been widely investigated as a strategy to mitigate HIBI. However, clinical trials aimed at optimising convective oxygen delivery have yielded neutral results. Advances in the understanding of HIBI pathophysiology suggest that impairments in the stages of the oxygen cascade pertaining to oxygen diffusion and cellular utilisation of oxygen should also be considered in identifying therapeutic strategies for the clinical management of HIBI patients. Culprit mechanisms for these impairments may include a widening of the diffusion barrier due to peri-vascular oedema and mitochondrial dysfunction. An integrated approach encompassing both intra-parenchymal and non-invasive neuromonitoring techniques may aid in detecting pathophysiologic changes in the oxygen cascade and enable patient-specific management aimed at reducing the severity of HIBI.

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Section: Discussionmentioning

confidence: 99%

Section: Stage 1: Convective Oxygen Deliverymentioning

confidence: 99%

Clinical targeting of the cerebral oxygen cascade to improve brain oxygenation in patients with hypoxic–ischaemic brain injury after cardiac arrest

et al. 2023

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“…A prospective cohort study done by Vaheersalo et al showed that moderate hypercapnia is associated with improved outcomes (OR=1.015; 95%CI 1.002 to 1.029) [ 39 ]. However, a recent RCT done by Eastwood investigating the effects of targeted mild hypercapnia and normocapnia did not show any significant difference in neurological outcomes between the two cohorts (RR=0.98; 95%CI 0.87 to 1.11) [ 7 ].…”

Section: Reviewmentioning

confidence: 99%

“…Cardiac rehabilitation has shown evidence to reduce mortality, improve quality of life, and cost-effectiveness [ 6 ]. Maintaining normocapnia in comatose OHCA survivors has improved neurological outcomes; however, the evidence is not conclusive [ 7 ]. Identifying and treating underlying adverse events like seizures with appropriate antiepileptic medications have shown overall improvements [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Unveiling Breakthroughs in Post-resuscitation Supportive Care for Out-of-Hospital Cardiac Arrest Survivors: A Narrative Review

Jagarlamudi,

Soni,

Ahmed

et al. 2023

Cureus

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Survivors of out-of-hospital cardiac arrest (OHCA) experience significant mortality rates and neurological impairment, potentially attributed to the hypoxic-ischemic injury sustained amid the cardiac arrest episode. Post-resuscitation care plays a crucial role in determining outcomes for survivors of OHCA. Supportive therapies have proven to be influential in shaping these outcomes. However, targeting higher blood pressure or oxygen levels during the post-resuscitative phase has not been shown to offer any mortality or neurological benefits. In terms of maintaining hemodynamic instability after resuscitation, it is recommended to use norepinephrine rather than epinephrine. While extracorporeal cardiopulmonary resuscitation has shown promising results, targeted temperature management has been found ineffective in improving outcomes despite its previous potential. This review also investigates various challenges and barriers associated with the practical implementation of these supportive therapies in clinical settings. The review also highlights areas ripe for future research and proposes potential directions to further enhance post-resuscitation supportive care for OHCA survivors.

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“…The Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest (TAME) trial [7] investigated whether targeting mild hypercapnia (TMH [PaCO 2 = 6.7-7.3 kPa]) compared to targeting normocapnia (TN [PaCO 2 = 4.7-6.0 kPa]) for 24 hours in comatose adults resuscitated after OHCA could improve neurological outcomes at six months. In this regard, hypercapnia increases cerebral blood ow [8], but hypercapnic acidosis is also believed to exert signi cant systemic haemodynamic effects [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Targeted mild hypercapnia after out-of-hospital cardiac arrest is associated with favourable cardiovascular effects. A sub-study of the TAME cardiac arrest trial.

Melberg

Flaa

Andersen

et al. 2023

Preprint

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Purpose: Hypercapnic acidosis may elicit detrimental haemodynamic effects in critically ill patients. We aimed to investigate the consequences of targeted mild hypercapnia (TMH) versus targeted normocapnia (TN) on pulmonary vascular resistance and right ventricular function in patients resuscitated from out-of-hospital cardiac arrest (OHCA). Methods: Single-centre, prospective, sub-study of the Targeted Therapeutic Mild Hypercapnia After Resuscitated Cardiac Arrest (TAME) trial. Patients were randomised to TMH (PaCO2 = 6.7–7.3 kPa) or TN (PaCO2 = 4.7-6.0 kPa) for 24 hours. Haemodynamic assessment was performed with right heart catheterisation and serial blood-gas analyses every 4th hour for 48 hours. Results: We studied 84 patients. Mean pH was 7.24 (95 % CI 7.22–7.30) and 7.32 (95 % CI 7.31–7.34) with TMH and TN, respectively (P-group < 0.001). Pulmonary vascular resistance index (PVRI), pulmonary artery pulsatility index, and right atrial pressure did not differ between groups (P-group > 0.05). Mean cardiac index was higher with TMH (P-group < 0.001): 2.0 (95 % CI 1.85–2.1) vs 1.6 (95 % CI 1.52–1.76) L/min/m2. Systemic vascular resistance index was 2579 dyne-sec/cm-5/ m2 (95 % CI 2356–2830) with TMH, and 3249 dyne-sec/cm-5/ m2 (95 % CI 2930 – 3368) with TN (P-group < 0.001). Stroke volumes (P-group = 0.013) and mixed venous oxygen saturation (P-group < 0.001) were higher in the TMH-group. Conclusion: In resuscitated OHCA patients, targeting mild hypercapnia did not increase PVRI or worsen right ventricular function compared to TN. TMH comparatively improved cardiac performance and mixed venous oxygen saturation. Trial registration number: NCT03114033

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Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest

Cited by 65 publications

References 38 publications

Clinical targeting of the cerebral oxygen cascade to improve brain oxygenation in patients with hypoxic–ischaemic brain injury after cardiac arrest

Clinical targeting of the cerebral oxygen cascade to improve brain oxygenation in patients with hypoxic–ischaemic brain injury after cardiac arrest

Unveiling Breakthroughs in Post-resuscitation Supportive Care for Out-of-Hospital Cardiac Arrest Survivors: A Narrative Review

Targeted mild hypercapnia after out-of-hospital cardiac arrest is associated with favourable cardiovascular effects. A sub-study of the TAME cardiac arrest trial.

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