Publication

• Title: Mechanical chest compressions and simultaneous defibrillation vs conventional cardiopulmonary resuscitation in out-of-hospital cardiac arrest: the LINC randomized trial
• Acronym: LINC (LUCAS in Cardiac Arrest)
• Year: 2014
• Journal published in: JAMA
• Citation: Rubertsson S, Lindgren E, Smekal D, et al. Mechanical chest compressions and simultaneous defibrillation vs conventional cardiopulmonary resuscitation in out-of-hospital cardiac arrest: the LINC randomized trial. JAMA. 2014;311(1):53-61.

Context & Rationale

• Background

  • Out-of-hospital cardiac arrest outcomes depend on early defibrillation and high-quality chest compressions with minimal interruptions.
  • Manual CPR quality is highly variable, deteriorates with rescuer fatigue, and is logistically challenging during transport and procedures.
  • Conventional ALS algorithms require pauses for rhythm analysis and defibrillation; even short pauses can reduce coronary and cerebral perfusion pressures.
  • Mechanical CPR devices (e.g., LUCAS) can provide consistent compressions and may increase chest compression fraction; they also enable compressions in environments where manual CPR is compromised.
  • Defibrillation during ongoing compressions is conceptually attractive for reducing peri-shock pauses, but the clinical value and safety of a timed shock strategy without rhythm confirmation were uncertain.
• Research Question/Hypothesis

  • Whether a prehospital “bundle” (mechanical chest compressions plus a defibrillation strategy intended to minimise pauses) improves early survival compared with conventional manual CPR.
  • Whether any early survival benefit translates into improved longer-term survival with favourable neurological outcome (CPC 1–2) at 6 months.
• Why This Matters

  • Mechanical CPR devices were being adopted for workflow and safety reasons; robust outcome evidence was required to justify routine use and guide EMS policy.
  • The tested intervention was a complex implementation bundle; clinicians needed to know whether it improved patient-centred outcomes rather than process metrics alone.
  • A neutral result would imply that delays, protocol features, or real-world deviations can negate theoretical haemodynamic advantages, shaping how (and whether) devices should be deployed.

Design & Methods

• Research Question: In adult out-of-hospital cardiac arrest with attempted resuscitation, does a mechanical CPR algorithm using the LUCAS device with a timed defibrillation strategy improve 4-hour survival compared with conventional manual CPR?
• Study Type:
  • Multicentre, individual patient randomised controlled trial (1:1 allocation), delivered in the prehospital setting (advanced life support EMS) with linked receiving hospitals.
  • Geography: 4 Swedish, 1 British, and 1 Dutch EMS systems; enrolment January 2008 to August 2012; follow-up completed February 2013.
  • Open-label (blinding not feasible), with objective primary outcome.
• Population:
  • Setting: out-of-hospital, EMS-treated cardiac arrest where the resuscitation attempt was considered appropriate by the attending crew.
  • Inclusion: adults (≥18 years) with unexpected out-of-hospital cardiac arrest.
  • Exclusion: traumatic arrest (including hanging), known pregnancy, body size too large or too small for the mechanical device.
  • Additional non-eligibility: defibrillated before the study device arrived on scene; crew-witnessed arrest with ROSC after immediate defibrillation.
  • Allocation: sealed opaque envelopes at the patient’s side (prehospital), used to randomise to one of two CPR algorithms.
• Intervention:
  • Device and workflow: manual compressions until deployment of the LUCAS mechanical chest compression device; mechanical compressions then initiated and continued.
  • Compression–shock algorithm: 3-minute cycles of mechanical compressions.
  • Timed defibrillation: first shock delivered at 90 seconds into the first 3-minute cycle, without rhythm analysis and without pausing compressions.
  • Ongoing rhythm management: rhythm analysis after each 3-minute cycle; if VF/VT, a new 3-minute cycle commenced and countershock delivered after 90 seconds of compressions (again without rhythm analysis and without pausing compressions).
  • Other ALS care: airway management, vascular access, and drugs per standard practice and guideline era (not protocolised by randomised arm beyond the CPR/defibrillation algorithm).
• Comparison:
  • Conventional CPR: manual CPR according to 2005 European Resuscitation Council guidelines as implemented locally.
  • Defibrillation/rhythm checks: rhythm analysis and defibrillation delivered per standard algorithm, with compressions paused for rhythm analysis and shock delivery (with attempts to minimise interruptions consistent with guideline era).
  • Post-resuscitation care: delivered according to local protocols (e.g., therapeutic hypothermia and coronary angiography/PCI where indicated), not randomised.
• Blinding: Unblinded (prehospital device deployment and algorithm made blinding infeasible); primary outcome (4-hour survival) was objective, while neurological outcome assessment could be susceptible to performance/detection effects.
• Statistics:
  • Power calculation: a total of 2500 patients were planned to detect a 6% absolute increase in 4-hour survival (from 25% to 31%) with 90% power at a 5% two-sided significance level (with a final primary threshold of P<0.048 reflecting the interim analysis plan).
  • Analysis type: intention-to-treat described as including all randomised patients except surviving patients who refused participation; missing outcomes were imputed as unfavourable (dead or CPC 3–4, as applicable).
• Follow-Up Period: outcomes reported to hospital discharge, 1 month, and 6 months (including Cerebral Performance Category).

Key Results

This trial was not stopped early. A planned interim analysis was performed (spring 2011) with continuation recommended; final enrolment was 2589 analysed patients (1300 intervention; 1289 comparison).

• The primary endpoint (4-hour survival) was virtually identical between groups, with confidence intervals excluding a clinically large absolute benefit (>3%).
• Longer-term survival and favourable neurological outcome (CPC 1–2 at 6 months) were not improved by the mechanical CPR + timed defibrillation strategy.
• The intervention altered CPR process (higher chest compression fraction in a 10% sample; markedly different defibrillation exposure), but this did not translate into outcome benefit.

Internal Validity

• Randomisation and allocation concealment:
  • 1:1 randomisation using sealed opaque envelopes at the patient’s side (prehospital), supporting concealment at the point of enrolment.
  • Envelope-based systems can be vulnerable to foreknowledge, but no manipulation was reported.
• Dropout and post-randomisation exclusions:
  • 2593 randomised; 4 withdrew consent after randomisation; 2589 included in the intention-to-treat analysis (1300 intervention; 1289 comparison).
  • Post-randomisation protocol violations of eligibility criteria occurred in 116 patients (68 intervention; 48 comparison) but were retained in the intention-to-treat analysis, preserving comparability.
  • For the primary outcome, 1 patient (intervention) and 3 patients (comparison) with missing 4-hour survival status were imputed as non-survivors.
• Performance and detection bias:
  • Unblinded delivery (device and algorithm), with potential for performance differences (e.g., workflow, drug timing, airway strategy).
  • Primary outcome (4-hour survival) is objective and relatively resistant to ascertainment bias.
  • Neurological outcomes (CPC) may be more vulnerable to unblinded assessment and to differences in post-resuscitation care pathways, although major post-resuscitation interventions were broadly similar.
• Protocol adherence and crossover:
  • Allocated intervention was received by 1227/1300 (intervention) and 1238/1289 (comparison).
  • Allocated intervention was not received by 73/1300 (intervention) and 51/1289 (comparison).
  • Crossovers occurred in both directions: 64 from intervention to manual CPR and 46 from comparison to mechanical CPR.
  • In the mechanical group, the full defibrillation algorithm was not adhered to in 24% of device-treated cases (largely due to issues with rhythm analysis or other algorithm steps).
• Baseline characteristics and illness severity:
  • Groups were well matched at baseline (e.g., mean age 69.0 vs 69.1 years; witnessed arrest 66% vs 65%; bystander CPR 57% vs 55%).
  • Initial rhythm distribution was similar (VF/pVT 29% vs 30%; asystole 47% vs 46%).
• Separation of the variable of interest (process measures):
  • Chest compression fraction (10% sample): 0.84 (intervention) vs 0.78 (comparison).
  • Defibrillation exposure differed substantially (number of defibrillations on scene: 0 in 308/1300 [24%] vs 697/1289 [54%]; 1 in 499/1300 [38%] vs 167/1289 [13%]; 4–20 in 209/1300 [16%] vs 233/1289 [18%]).
  • Time to first defibrillation was later in the intervention algorithm (median 17 minutes [IQR 12–22] vs 15.5 minutes [IQR 11–23.5]).
• Timing and “dose” of intervention:
  • The tested strategy required device deployment and then a timed defibrillation approach (first shock at 90 seconds into a 3-minute compression cycle), which can delay early shock delivery in patients with shockable rhythms.
  • The intervention therefore combined potential benefits (fewer pauses, higher compression fraction) with potential harms (later defibrillation and possible unnecessary shocks), complicating causal attribution to “mechanical compressions” alone.
• Statistical rigour:
  • Sample size target was achieved (planned 2500; analysed 2589).
  • Primary analysis used Fisher exact testing with a prespecified significance threshold reflecting the interim plan (P<0.048); confidence intervals were reported as treatment (risk) differences.
  • Missing outcomes were imputed as unfavourable, a conservative approach for survival/neurological endpoints.

Conclusion on Internal Validity: Overall, internal validity appears moderate: randomisation was robust and primary outcomes were objective with low missingness, but the open-label bundle intervention, protocol deviations, and bidirectional crossover dilute treatment contrast and limit inference about the device itself versus the defibrillation/workflow strategy.

External Validity

• Population representativeness:
  • Participants were typical EMS-treated adult OHCA patients in high-resource systems (multi-country ALS EMS), with high proportions of witnessed arrest and bystander CPR.
  • Key exclusions (trauma, pregnancy, body size constraints, defibrillation before device arrival, and crew-witnessed immediate ROSC after defibrillation) remove clinically important subgroups, including very early-shock patients with high baseline survival probability.
• Applicability to practice:
  • The intervention tested an explicit algorithm (timed shock at 90 seconds without rhythm analysis) that is not the only way mechanical CPR is used in modern systems; generalisation depends on how closely local practice matches this bundle.
  • Manual CPR comparator reflected the 2005 guideline era; contemporary CPR strategies (and post-resuscitation care) may differ, potentially shifting the balance of benefit/harm for any device-enabled approach.
  • Findings most directly apply to EMS systems capable of training, device maintenance, and structured deployment; generalisability to resource-limited settings is constrained by cost and training requirements.

Conclusion on External Validity: Generalisability is moderate: results apply well to advanced prehospital systems considering routine mechanical CPR deployment, but are tightly linked to the specific bundle tested and to exclusion of certain early-defibrillation subgroups.

Strengths & Limitations

• Strengths:
  • Large pragmatic, multicentre prehospital randomised trial (n=2589) across multiple EMS systems and countries.
  • Clinically meaningful endpoints, including 6-month survival and neurological outcome (CPC).
  • Prespecified sample size and interim plan; objective primary outcome with minimal missingness.
  • Device safety and implementation issues were described (crossover, adherence, device-related adverse events), aiding real-world interpretation.
• Limitations:
  • Open-label delivery with potential performance bias; neurological outcome assessment may be susceptible to unblinded influences.
  • Intervention was a bundle (mechanical compressions + timed shocks without rhythm analysis + workflow changes), limiting attribution of effects specifically to mechanical compressions.
  • Substantial deviations and crossovers (73 and 51 not receiving allocated treatment; 64 and 46 crossovers), reducing treatment separation and potentially biasing towards the null.
  • CPR quality measures were formally quantified in only a 10% sample, limiting inference about compression depth/rate and interruption patterns across the full cohort.
  • Comparator reflected 2005 guideline era; changes in modern ALS and post-resuscitation care may alter applicability.

Interpretation & Why It Matters

• Routine practice

  Routine implementation of a LUCAS-based mechanical CPR + timed defibrillation algorithm did not improve early survival or longer-term favourable neurological outcomes compared with conventional manual CPR.
• Implementation science message

  Mechanical CPR does not “automatically” translate into better outcomes; deployment delays, protocol features (e.g., timed shocks without rhythm confirmation), and real-world deviations can plausibly offset any haemodynamic advantage.
• Where the device may still matter

  The neutral result strengthens the case for selective use (transport, cath lab, prolonged CPR, ECPR cannulation) rather than routine deployment, with an emphasis on minimising delays and ensuring protocol fidelity.

Controversies & Subsequent Evidence

• The intervention tested a timed shock strategy delivered during compressions without prior rhythm analysis (first shock at 90 seconds of a 3-minute cycle); correspondence highlighted the risk of unnecessary shocks and questioned electrophysiological plausibility/optimisation of shock timing relative to compression phase. ¹
• Later large pragmatic trials of routine mechanical CPR deployment in OHCA (using different devices/implementation strategies) reported broadly neutral survival effects, reinforcing that mechanical CPR is not a universal “mortality-improving” intervention when used routinely.
• Modern international guidance has converged on avoiding routine mechanical CPR deployment while supporting selective use when high-quality manual compressions are difficult or unsafe (e.g., transport, angiography/PCI, ECPR cannulation), emphasising careful implementation to prevent delays.

Summary

• LINC randomised 2593 OHCA patients; 2589 were analysed (1300 mechanical CPR + timed defibrillation vs 1289 manual CPR).
• Primary outcome (4-hour survival) was identical: 23.6% vs 23.7% (risk difference -0.05%; 95% CI -3.3% to 3.2%; P>.99).
• There was no improvement in 6-month survival (8.5% vs 8.1%) or 6-month survival with CPC 1–2 (8.5% vs 7.6%).
• Process separation existed (chest compression fraction 0.84 vs 0.78 in a 10% sample; very different defibrillation exposure), but the intervention also delayed first defibrillation (median 17 vs 15.5 minutes).
• Device-related adverse events were reported (23 events per 1282 device uses), underscoring that device implementation is not risk-free.

Further Reading

Other Trials

• 2015Perkins GD, Lall R, Quinn T, et al. Mechanical versus manual chest compressions for out-of-hospital cardiac arrest (PARAMEDIC): a pragmatic, cluster randomised controlled trial. Lancet. 2015;385(9972):947-955.
• 2014Wik L, Olsen JA, Persse D, et al. Manual vs integrated automatic load-distributing band CPR with equal survival after out of hospital cardiac arrest: the randomised CIRC trial. Resuscitation. 2014;85(6):741-748.
• 2006Hallstrom A, Rea TD, Sayre MR, et al. Manual chest compression vs use of an automated mechanical chest compression device in out-of-hospital cardiac arrest: a randomised trial. JAMA. 2006;295(22):2620-2628.
• 2014Rubertsson S, Lindgren E, Smekal D, et al. Mechanical chest compressions and simultaneous defibrillation vs conventional cardiopulmonary resuscitation in out-of-hospital cardiac arrest: the LINC randomized trial. JAMA. 2014;311(1):53-61.

Systematic Review & Meta Analysis

• Not reportedCarron P-N, Yersin B. Cardiopulmonary Resuscitation With Mechanical Chest Compressions and Simultaneous Defibrillation. JAMA. 2014;311(21):2234-2235.

Observational Studies

• 2010Wagner H, Terkelsen CJ, Friberg H, et al. Cardiac arrest in the catheterisation laboratory: a 5-year experience of using mechanical chest compressions to facilitate percutaneous coronary intervention during prolonged resuscitation efforts. Resuscitation. 2010;81(4):383-387.

Guidelines

• 2025European Resuscitation Council. European Resuscitation Council Guidelines 2025: Adult advanced life support. Resuscitation. 2025.
• 2025American Heart Association. Part 9: Adult Advanced Life Support: 2025 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2025.
• 2025American Heart Association. 2025 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: Executive Summary. Circulation. 2025.
• 2020American Heart Association. Part 3: Adult Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2020.

Notes

• LINC tested a specific bundle (mechanical compressions plus timed shocks without rhythm analysis); extrapolating to other deployment strategies should account for workflow delays, training, and device fit issues.

Overall Takeaway

LINC is “landmark” because it subjected a mechanistically appealing but implementation-heavy strategy (mechanical CPR plus a timed defibrillation approach intended to minimise pauses) to a large, pragmatic prehospital randomised test. Despite measurable process differences, it demonstrated no improvement in early survival or longer-term favourable neurological outcomes, reinforcing that mechanical CPR should be considered a selective tool rather than a routine survival-improving intervention.

Bibliography

• 1Carron P-N, Yersin B. Cardiopulmonary Resuscitation With Mechanical Chest Compressions and Simultaneous Defibrillation. JAMA. 2014;311(21):2234-2235.