Hypoxia, Timing, and Why HBOT Should Never Be a Last Resort

Hypoxia, Timing, and Why HBOT Should Never Be a Last Resort

Hypoxia is the quiet thread that runs through nearly every condition eventually referred for hyperbaric oxygen therapy. Long before a wound becomes gangrenous, before radionecrosis becomes structurally entrenched, or before osteomyelitis evolves into a resection-driven disease, tissues endure a prolonged state of microvascular insufficiency, low oxygen tension, and metabolic distress. This “pre-failure physiology” is where biology is still plastic. Mitochondria remain salvageable, inflammatory pathways can still be modulated, and microcirculatory beds have not yet collapsed into irreversible dysfunction. Waiting for overt necrosis or catastrophic infection is not clinical prudence — it is the loss of the therapeutic window in which HBOT has its greatest effect.

In the 4th quarter edition of UHM Dick Clarke presents a review on transcutaneous oximetry. It makes the point plainly: the central determinant of HBOT responsiveness is reversible hypoxia — a tissue environment where oxygen delivery is inadequate, but still capable of being restored if addressed early. Early HBOT capitalizes on this reversibility, because hyperbaric exposure increases oxygen diffusion, stimulates VEGF-driven angiogenesis, mobilizes stem cells, accelerates endothelial and fibroblast proliferation, and enhances immune function (Sheikh 2000; Lee 2006; Thom 2006). Once microvascular failure crosses into non-reversible ischemia or dense fibrosis, these pathways do not activate with the same magnitude.

Clarke’s work demonstrates that persistent peri-lesion hypoxia is one of the strongest markers of impaired healing, and that its correction through HBOT requires underlying physiologic capacity — intact pulmonary function, adequate macrovascular inflow, and functional microcirculation. Transcutaneous oximetry delineates this capacity and shows where the therapeutic window remains open. When tcpO₂ values rise appropriately in response to oxygen challenge or early hyperbaric dosing, it confirms that tissues are still recruitable. When HBOT is delayed until months of chronic hypoxia have carved out irreversible pathology, those same tissues predictably fail to respond. HBOT has not failed; the timing has.

The problem is systemic. Many institutions still treat HBOT as if it were a salvage maneuver rather than a biologic conditioning therapy. They wait until ulcers are Wagner Grade 4 or 5, until radiation injury has hardened into high-grade soft-tissue necrosis, or until chronic infections have already required multiple surgical resections. This timing bias is reinforced by reimbursement policies that privilege late-stage complexity, by limited chamber capacity that forces triage toward the most desperate cases, and by the entrenched misconception that HBOT should only be offered when “nothing else works.”

The Clarke paper reinforces how harmful this delay is. In diabetic foot ulcers, 70% remain unhealed after 20 weeks of standard care; 20% remain open after a year; and infection-driven amputations remain distressingly common. These numbers represent months of unaddressed hypoxia — a condition HBOT is designed to reverse early, not clean up after late. TcpO₂-guided care demonstrates that patients who show reversible hypoxia early in their course not only benefit more from HBOT, but do so more cost-effectively. Conversely, using HBOT only after structural deterioration has progressed results in lower responsiveness, higher treatment burden, and increased health-system expenditure, all while asking hyperbaric teams to salvage biology long past its turning point.

Late HBOT also carries a safety penalty that is often overlooked. When patients arrive at the chamber as a last resort, they are frequently immunocompromised, hemodynamically unstable, burdened by polypharmacy, or suffering from advanced metabolic stress. Complications are more likely under these conditions, yet when they occur, the therapy is too often blamed rather than the delay that made the patient fragile in the first place. Early HBOT reduces this risk by stabilizing physiology before instability evolves.

A more rational model — one supported both by mechanistic science and the practical screening framework described in the attached Clarke review — is to integrate HBOT at the earliest point where reversible hypoxia is identified. TcpO₂ values below 40 mmHg represent impaired healing; below 30 mmHg, critical ischemia dominates the biology. When a patient demonstrates that their hypoxia is reversible on oxygen challenge or early hyperbaric exposure, they should be treated then — not after months of failed standard care. This is precisely the period where angiogenesis can still be induced, where fibroblasts respond robustly, and where microcirculatory repair improves global wound biomechanics.

Early HBOT is not a luxury or an escalation step; it is a logical response to physiologic deterioration that is already well underway. When applied early, HBOT reduces long-term costs, shortens treatment timelines, improves limb salvage rates, and prevents the cascade from hypoxia to infection to amputation. When relegated to a last-ditch effort, its therapeutic effect is sharply blunted, and teams are set up to appear ineffective against disease processes that should have been intercepted much sooner.

The phrase “Hypoxia – early recognition is key” should therefore be understood not as a slogan but as a foundational safety and quality principle. It speaks to biology, but it also speaks to system design. If institutions build pathways where meeting objective criteria — such as reversible hypoxia measured by tcpO₂ — automatically triggers early HBOT referral, outcomes improve and costs fall. If they instead wait for failure, they will predictably continue to see HBOT underperform, not because the therapy is weak, but because it was introduced far too late in the disease arc.

In this framing, HBOT is not a last resort; it is one of the first rational interventions when hypoxia and inflammation begin their destructive interplay. Early action preserves biology. Late action merely chases collapse.