Publication

• Title: Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries
• Acronym: None
• Year: 1994
• Journal published in: The New England Journal of Medicine
• Citation: Bickell WH, Wall MJ Jr, Pepe PE, Martin RR, Ginger VF, Allen MK, Mattox KL. Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med. 1994;331(17):1105-9.

Context & Rationale

• Background

  In the early 1990s, standard trauma algorithms commonly prioritised rapid restoration of “normal” blood pressure with large-volume isotonic crystalloid before haemorrhage control in hypotensive trauma.
  Experimental and physiological work raised concern that raising arterial pressure before surgical control could exacerbate ongoing haemorrhage, dislodge early thrombus (“hydraulic disruption”), and dilute coagulation factors, while prehospital infusion could also prolong scene time.
• Research Question/Hypothesis

  In hypotensive patients with penetrating torso injury, does delaying preoperative intravenous fluid resuscitation until operative intervention improve survival compared with immediate prehospital and emergency-centre fluid resuscitation?
• Why This Matters

  This was a landmark clinical test of the “permissive hypotension / delayed resuscitation” concept in penetrating haemorrhage, challenging long-standing assumptions about early crystalloid as an unqualified good in shock.

Design & Methods

• Research Question: Whether delaying intravenous fluid resuscitation until operative intervention improves survival to hospital discharge versus immediate fluid resuscitation in hypotensive penetrating torso trauma.
• Study Type: Prospective, controlled, single-system prehospital-to-trauma-centre trial; alternate-day (even/odd day of month) assignment (quasi-randomised); unblinded; conducted across an urban EMS system and a single trauma centre.
• Population:
  • Setting: City of Houston EMS system and Ben Taub General Hospital (Baylor College of Medicine) trauma care pathway (prehospital, emergency centre, operating theatre).
  • Inclusion: penetrating injury to the torso (e.g., chest/abdomen/neck or groin exploration as operative indications) with prehospital systolic blood pressure <90 mm Hg (including “no measurable blood pressure”) at initial on-scene assessment; age ≥16 years.
  • Key exclusions from outcome analysis: Revised Trauma Score (RTS) of 0 at the scene; fatal gunshot wound to the head; minor injuries not requiring operative intervention (patients not requiring operation were excluded from analytic cohort).
  • Analysed cohort: 598 patients (of 1069 screened over 37 months).
• Intervention:
  • Immediate-resuscitation group: standard paramedical protocol plus rapid infusion of isotonic crystalloid (Ringer’s acetate) in the prehospital setting and continued crystalloid infusion in the emergency centre for systolic blood pressure >100 mm Hg (plus packed red cells when necessary per standard criteria).
  • Intraoperative management (both groups): once in theatre and under general anaesthesia, intravenous crystalloid and packed red cells were given as needed to maintain systolic arterial pressure ~100 mm Hg, haematocrit ≥25%, and urine output ≥50 mL/hour; hetastarch occasionally used as additional intravascular volume expander.
• Comparison:
  • Delayed-resuscitation group: identical clinical pathway except no intravenous fluid bolus/resuscitation before operative intervention.
  • Intravenous access was established prehospital; catheters were capped and flushed with 1–2 mL of 1% heparin in normal saline; any additional emergency-centre catheters were kept patent with Ringer’s acetate at 10 mL/hour (line patency rather than resuscitation).
  • Intraoperative resuscitation targets were the same as the intervention group after arrival in theatre.
• Blinding: None (prehospital and in-hospital staff were necessarily aware of fluid strategy; primary outcome was objective).
• Statistics: A priori sample size planned at ~600 patients to detect a 10–15 percentage-point improvement in survival (assuming 35% mortality with standard preoperative fluid resuscitation), with two-sided α=0.05 and β=0.20 (80% power); one interim analysis used a stringent Haybittle–Peto boundary; analyses reported as intention-to-treat (by assigned group), using χ² for categorical comparisons and Mann–Whitney U (or rank-sum) for continuous variables.
• Follow-Up Period: In-hospital to discharge (survival to discharge; postoperative complications assessed in operative survivors).

Key Results

This trial was not stopped early. One interim analysis was performed during the 37-month study period; final analyses used conventional two-sided P<0.05 significance.

• Delayed resuscitation improved survival to discharge: 70% vs 62% (P=0.04; survival 95% CI 65–75% vs 57–68%).
• The intervention created large, clinically meaningful separation in preoperative crystalloid exposure (prehospital 870 ± 667 mL vs 92 ± 309 mL; trauma centre 1608 ± 1201 mL vs 283 ± 722 mL; both P<0.001).
• Immediate fluids increased systolic BP at arrival (79 ± 46 vs 72 ± 43 mm Hg; P=0.02) but were associated with markedly prolonged prothrombin time (14.1 ± 1.6 vs 11.4 ± 1.8 sec; P<0.001), supporting a plausible harm pathway (dilutional/haemostatic impairment) in uncontrolled haemorrhage.

Internal Validity

• Randomisation and allocation: Assignment by even/odd day of month (alternate-day) was pragmatic but not truly random; allocation concealment was not possible, raising risk of selection and performance bias.
• Dropout/exclusions: 1069 consecutive hypotensive penetrating torso trauma patients were screened; 172 with RTS=0 and 299 with minor injuries not requiring operation were excluded from outcome analysis, leaving 598 analysed (309 immediate; 289 delayed); exclusions after initial screening can introduce bias if exclusions differ by group.
• Baseline balance: Groups were broadly comparable (age 31 ± 11 vs 31 ± 10 years; male 88% vs 91%; SBP at scene 58 ± 35 vs 59 ± 34 mm Hg; Injury Severity Score 26 ± 14 in both; gunshot wounds 65% vs 67%).
• Protocol adherence and separation: Strong separation in the primary exposure (prehospital Ringer’s acetate 870 ± 667 mL vs 92 ± 309 mL; trauma-centre Ringer’s acetate 1608 ± 1201 vs 283 ± 722 mL).
• Crossover/contamination: The delayed group still received non-trivial prehospital/trauma-centre fluid on average (92 mL and 283 mL respectively), implying some protocol leakage; the magnitude, indications, and timing of these deviations are not fully granular.
• Timing and co-interventions: Scene interval differed (9 ± 8 vs 7 ± 6 minutes), consistent with potential operational effects of administering fluids; intraoperative interval was longer in delayed group (134 ± 101 vs 114 ± 105 minutes; P=0.028), which could reflect case-mix variation or downstream operational differences.
• Outcome assessment: Primary endpoint (survival to discharge) is objective and less vulnerable to ascertainment bias; complication endpoints were clinically defined and assessed prospectively among operative survivors.
• Statistical rigour: Power and interim analysis strategy were prespecified; analyses were reported as intention-to-treat by assigned group; however, the quasi-randomised design and post-screening exclusions mean residual confounding cannot be eliminated.

Conclusion on Internal Validity: Moderate. The exposure separation and objective primary outcome support credibility, but alternate-day (non-concealed) assignment, lack of blinding, and analytic exclusions after screening increase susceptibility to bias and confounding.

External Validity

• Population representativeness: Predominantly young, male, urban penetrating trauma with short prehospital intervals (response ~8 minutes; transport ~12 minutes); applicability strongest to similar systems and injury patterns.
• Setting dependence: Findings may not translate to rural/prolonged transport settings where longer “no fluid” intervals could be harmful, particularly if delays to haemorrhage control are substantial.
• Injury-pattern limitations: The trial informs penetrating torso haemorrhage without emphasis on traumatic brain injury (TBI); permissive hypotension is typically inappropriate when cerebral perfusion is threatened.
• Era effects: Conducted before modern damage-control resuscitation norms (early balanced blood products, tranexamic acid, widespread point-of-care coagulation testing, and prehospital blood components), limiting direct extrapolation to contemporary haemostatic strategies.

Conclusion on External Validity: Moderate. Highly applicable to short-transport penetrating torso haemorrhage in systems similar to the study setting, but generalisability is limited for blunt trauma, TBI, prolonged prehospital times, and contemporary blood-component resuscitation pathways.

Strengths & Limitations

• Strengths: Clinically meaningful primary endpoint; large cohort for a prehospital trauma trial; pragmatic implementation across an entire EMS/trauma pathway; strong protocol separation in preoperative fluid exposure; physiologically coherent laboratory differences supportive of mechanism.
• Limitations: Quasi-random (alternate-day) allocation without concealment; unblinded delivery; analytic exclusions after screening; potential confounding by operational factors (e.g., scene time); single-city/single-centre context; fluid strategy tested was “near-zero” versus targeting SBP >100 mm Hg (not a modern “controlled resuscitation” target).

Interpretation & Why It Matters

• A paradigm shift

  The trial provided high-profile clinical evidence that aggressive preoperative crystalloid aimed at “normalising” blood pressure can be harmful in uncontrolled penetrating haemorrhage, supporting delayed/controlled resuscitation until haemostasis.
• The target matters

  Immediate resuscitation pursued systolic BP >100 mm Hg preoperatively; contemporary permissive hypotension typically targets lower pressures (e.g., SBP ~80–90) in patients without TBI, suggesting the trial may demonstrate harm from over-resuscitation rather than harm from “any fluid”.
• Mechanistic signal

  Higher arrival SBP (79 vs 72 mm Hg) accompanied by worse coagulation indices (PT 14.1 vs 11.4 sec) supports a plausible pathway linking early crystalloid to haemostatic impairment and worse outcomes when bleeding is not yet controlled.

Controversies & Subsequent Evidence

• Design critique: Alternate-day assignment without concealment and unblinded delivery create risk of systematic differences between groups (including operational behaviours); the modest absolute survival difference (8 percentage points) could be vulnerable to residual confounding even with similar baseline severity.
• Operational confounding: The delayed group had a shorter scene interval (7 ± 6 vs 9 ± 8 minutes), so part of the observed benefit could plausibly relate to faster transport/earlier haemorrhage control rather than the fluid exposure alone.
• Randomised follow-up trials show mixed replication: Subsequent controlled/hypotensive resuscitation trials in haemorrhagic shock did not consistently reproduce a mortality benefit and often focused on different targets/settings (e.g., ED SBP 70 vs 100) ¹²³⁴.
• Synthesis of evidence: Meta-analysis of hypotensive resuscitation strategies suggests potential reductions in mortality and transfusion requirements, but heterogeneity of targets, injury patterns, and resuscitation era limits certainty and generalisability ⁵.
• Guideline incorporation with caveats: Contemporary major-haemorrhage trauma guidelines/protocols broadly support avoiding excessive crystalloid and using permissive hypotension until haemorrhage control in patients without suspected TBI, embedding Bickell’s core principle while shifting focus towards balanced blood-component and haemostatic resuscitation ⁶⁷.

Summary

• Prospective alternate-day trial in hypotensive penetrating torso trauma comparing immediate crystalloid resuscitation versus delayed resuscitation until operative intervention.
• Delayed resuscitation improved survival to discharge: 70% vs 62% (P=0.04).
• The intervention achieved major separation in preoperative crystalloid exposure (prehospital 870 vs 92 mL; trauma centre 1608 vs 283 mL; both P<0.001).
• Immediate fluids increased arrival SBP but were associated with worse early coagulation indices (PT 14.1 vs 11.4 sec; P<0.001), supporting a biologically plausible harm mechanism.
• Internal validity is limited by quasi-random allocation and lack of concealment/blinding, but the objective primary outcome and clear protocol separation make the findings influential.

Further Reading

Other Trials

• 2002Dutton RP, Mackenzie CF, Scalea TM. Hypotensive resuscitation during active hemorrhage: impact on in-hospital mortality. J Trauma. 2002;52(6):1141-6.
• 2011Morrison CA, Carrick MM, Norman MA, Scott BG, Welsh FJ, Tsai P, Liscum KR, Wall MJ Jr, Mattox KL. Hypotensive resuscitation strategy reduces transfusion requirements and severe postoperative coagulopathy in trauma patients with hemorrhagic shock: preliminary results of a randomized controlled trial. J Trauma. 2011;70(3):652-63.
• 2015Schreiber MA, Meier EN, Tisherman SA, Kerby JD, Newgard CD, Brasel KJ, et al. A controlled resuscitation strategy is feasible and safe in hypotensive trauma patients: results of a prospective randomized pilot trial. J Trauma Acute Care Surg. 2015;78(4):687-97.
• 2016Carrick MM, Morrison CA, Tapia NM, Grové SA, Norman MA, Scott BG, Welsh FJ, Liscum KR, Wall MJ Jr, Mattox KL. Intraoperative hypotensive resuscitation for patients undergoing laparotomy or thoracotomy for trauma: early termination of a randomized prospective clinical trial. J Trauma Acute Care Surg. 2016;80(6):886-96.
• 1992Martin RR, Bickell WH, Pepe PE, Burch JM, Mattox KL. Prospective evaluation of preoperative fluid resuscitation in hypotensive patients with penetrating truncal injury: a preliminary report. J Trauma. 1992;33(3):354-61.

Systematic Review & Meta Analysis

• 2018Tran A, Yates J, Lau A, Lampron J, Matar M, Dhillon NK, et al. Permissive hypotension: a systematic review and meta-analysis of randomized controlled trials. J Trauma Acute Care Surg. 2018;84(5):802-8.
• 2018Owattanapanich N, Chittawatanarat K, Benyakorn T, Sirikun J. Risks and benefits of hypotensive resuscitation in patients with traumatic hemorrhagic shock: a meta-analysis. Scand J Trauma Resusc Emerg Med. 2018;26(1):107.
• 2014Wang CH, Hsieh WH, Chou HC, Huang YS, Shen JH, Yeo YH, Chang HE, Chen SC. Liberal versus restricted fluid resuscitation strategies in trauma patients: a systematic review and meta-analysis of randomized controlled trials and observational studies. Crit Care Med. 2014;42(4):954-61.
• 2022Safiejko K, Smereka J, Lukowska M, Szarpak L. Effect of hypotensive versus conventional resuscitation strategies in traumatic hemorrhagic shock: a systematic review and meta-analysis. Cardiol J. 2022;29(2):250-62.
• 2018Albreiki M, Middleton PM, Wilson KL, et al. Permissive hypotensive resuscitation in adult patients with traumatic haemorrhagic shock: a systematic review. Eur J Trauma Emerg Surg. 2018;44(2):191-202.

Observational Studies

• 2011Haut ER, Kalish BT, Cotton BA, Efron DT, Haider AH, Stevens KA, Kieninger AN, Cornwell EE 3rd, Chang DC. Prehospital intravenous fluid administration is associated with higher mortality in trauma patients: a National Trauma Data Bank analysis. Ann Surg. 2011;253(2):371-7.
• 2015Geeraedts LMG Jr, Pothof LA, Caldwell E, de Lange-de Klerk ESM, D’Amours SK. Prehospital fluid resuscitation in hypotensive trauma patients: do we really need fluids? Injury. 2015;46(1):4-9.
• 2019Hussmann B, Lefering R, Waydhas C, Ruchholtz S, Wafaisade A. Enhanced prehospital volume therapy does not lead to improved outcomes in severely injured patients with severe traumatic brain injury. BMC Emerg Med. 2019;19(1):13.
• 2023Deeb AP, Rathi N, Sakran JV, et al. Association of prehospital crystalloid resuscitation with outcomes in trauma patients: an analysis of a national cohort. J Am Coll Surg. 2023;236(5):873-883.e2.

Guidelines

• 2024LaGrone L, Galvagno SM Jr, Weinberg JA, et al. American Association for the Surgery of Trauma/American College of Surgeons clinical protocol for damage-control resuscitation. J Trauma Acute Care Surg. 2024;96(4):e93-e116.
• 2024McMullan JT, Guyette FX, Martin-Gill C, et al. NAEMSP position statement and resource document: Prehospital trauma resuscitation compendium. Prehosp Emerg Care. 2024;28(6):905-932.
• 2023Rossaint R, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernández-Mondéjar E, et al. The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition. Crit Care. 2023;27(1):80.
• 2019Spahn DR, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernández-Mondéjar E, et al. The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition. Crit Care. 2019;23(1):98.
• 2009Cotton BA, Guy JS, Morris JA Jr, Abumrad NN. The cellular, metabolic, and systemic consequences of aggressive fluid resuscitation strategies. J Trauma. 2009;66(3):S59-S70.

Notes

• The Bickell strategy is best interpreted as avoiding aggressive crystalloid to “normalise” blood pressure before haemostasis in penetrating haemorrhage; modern implementations typically pair permissive hypotension with early haemostatic resuscitation and explicit avoidance in suspected TBI.

Overall Takeaway

In hypotensive penetrating torso trauma with rapid access to definitive haemorrhage control, delaying preoperative crystalloid resuscitation improved survival to hospital discharge compared with immediate fluid aimed at normalising blood pressure. Despite important internal-validity limitations (alternate-day assignment and lack of concealment), the trial reshaped trauma resuscitation by providing a clinically grounded rationale for permissive hypotension and avoidance of excessive crystalloid prior to haemostasis.

Bibliography

• 1.Dutton RP, Mackenzie CF, Scalea TM. Hypotensive resuscitation during active hemorrhage: impact on in-hospital mortality. J Trauma. 2002;52(6):1141-6.
• 2.Morrison CA, Carrick MM, Norman MA, Scott BG, Welsh FJ, Tsai P, Liscum KR, Wall MJ Jr, Mattox KL. Hypotensive resuscitation strategy reduces transfusion requirements and severe postoperative coagulopathy in trauma patients with hemorrhagic shock: preliminary results of a randomized controlled trial. J Trauma. 2011;70(3):652-63.
• 3.Schreiber MA, Meier EN, Tisherman SA, Kerby JD, Newgard CD, Brasel KJ, et al. A controlled resuscitation strategy is feasible and safe in hypotensive trauma patients: results of a prospective randomized pilot trial. J Trauma Acute Care Surg. 2015;78(4):687-97.
• 4.Carrick MM, Morrison CA, Tapia NM, Grové SA, Norman MA, Scott BG, Welsh FJ, Liscum KR, Wall MJ Jr, Mattox KL. Intraoperative hypotensive resuscitation for patients undergoing laparotomy or thoracotomy for trauma: early termination of a randomized prospective clinical trial. J Trauma Acute Care Surg. 2016;80(6):886-96.
• 5.Tran A, Yates J, Lau A, Lampron J, Matar M, Dhillon NK, et al. Permissive hypotension: a systematic review and meta-analysis of randomized controlled trials. J Trauma Acute Care Surg. 2018;84(5):802-8.
• 6.Rossaint R, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernández-Mondéjar E, et al. The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition. Crit Care. 2023;27(1):80.
• 7.LaGrone L, Galvagno SM Jr, Weinberg JA, et al. American Association for the Surgery of Trauma/American College of Surgeons clinical protocol for damage-control resuscitation. J Trauma Acute Care Surg. 2024;96(4):e93-e116.