The patient required full hemodynamic, metabolic, and respiratory support from the time of admission. Early hemodynamic instability was managed with noradrenaline (norepinephrine) infusion at an approximate dose of 0.05 - 0.1 µg/kg/min, which was subsequently tapered as perfusion and metabolic status improved following initiation of extracorporeal support. Respiratory support consisted of supplemental non-invasive oxygen therapy to manage hypoxemic respiratory dysfunction in the context of mild ARDS; the patient did not require prolonged invasive ventilation [3][10].

Fluid resuscitation was performed with balanced isotonic crystalloid, titrated according to hemodynamic parameters, urine output, and evolving abdominal physiology. Given the severity of necrotizing pancreatitis and the risk of secondary infectious complications, empiric antimicrobial therapy with meropenem 20 mg/kg intravenously every 8 hours was administered. Nutritional management emphasized strict lipid restriction; parenteral lipid administration was avoided during the acute phase, and nutritional support was advanced cautiously as the patient stabilized.

Simultaneous and aggressive pharmacologic lipid reduction was initiated. A continuous intravenous insulin infusion was commenced, targeting euglycemia, with the additional aim of suppressing hepatic VLDL synthesis and stimulating LPL activity [6]. Intravenous unfractionated heparin was administered concurrently to mobilize endothelial LPL into the systemic circulation, consistent with its established use in HTG-AP, although it is acknowledged that this strategy is most effective when residual LPL activity is present and may have limited efficacy in FCS [6]. Oral fenofibrate was commenced via nasogastric tube to enhance LPL expression and reduce VLDL production [12]. Oral fat intake was withheld entirely, and parenteral lipid administration was avoided during the acute phase to eliminate exogenous chylomicron substrate.

Regarding empiric antimicrobial therapy, meropenem was selected, given the severity of necrotizing pancreatitis and the associated risk of secondary infection. It is acknowledged that prophylactic antibiotic use in necrotizing pancreatitis without documented infection remains debated in current guidelines, and the decision to treat empirically in this case was driven by clinical severity and multi-organ compromise rather than microbiological confirmation [3].

Despite this multimodal pharmacologic strategy, repeated serum triglyceride measurements over the ensuing 24 - 48 hours demonstrated no meaningful reduction. This lack of response was clinically interpreted as consistent with absent or severely deficient functional LPL activity, reinforcing the suspicion of FCS [4][7].

The failure to achieve triglyceride reduction despite maximal pharmacologic intervention was not a failure of supportive care—it was a failure of lipid clearance. This distinction is critical to the subsequent therapeutic decision.

Therapeutic plasma exchange operates through the non-selective removal and replacement of a large volume of the patient’s plasma. Unlike membrane-based CRRT, TPE separates plasma from cellular blood components using either centrifugation or membrane filtration techniques and replaces it with fresh frozen plasma (FFP) and/or albumin. This process is capable of removing large molecular weight structures, including chylomicrons, VLDL, inflammatory mediators carried by lipoproteins, and other high molecular weight toxins [8][9][15].

The American Society for Apheresis (ASFA) 2010 guidelines classify TPE as a Category I-II intervention for severe hypertriglyceridemia-induced pancreatitis, representing conditions in which apheresis is accepted as first-line therapy or as second-line therapy when other treatments have failed [16]. Given the persistent critical hypertriglyceridemia and ongoing multi-organ injury despite maximal pharmacological therapy and CRRT, the clinical team escalated management to urgent TPE.

Given persistent extreme hypertriglyceridemia despite intensive medical therapy and CRRT-supported metabolic stabilization, therapeutic plasma exchange was initiated. Two TPE sessions were performed on consecutive days, each exchanging approximately one plasma volume, with 5% albumin used as the replacement solution. The same central extracorporeal vascular access established for CRRT was utilized for both sessions. No major TPE-related adverse events were documented, including episodes of hypotension, hypocalcemia, citrate-related symptoms, allergic reactions, or circuit interruption [8][15][17].

The biochemical response to TPE was rapid and dramatic. Triglyceride levels remained critically elevated despite intensive medical therapy and CRRT, but fell sharply after initiation of therapeutic plasma exchange, decreasing to approximately 3500 mg/dL after the first session and approximately 300 mg/dL after the second session, with subsequent maintenance at <200 mg/dL during recovery—an overall reduction exceeding 98% from admission levels (Figure 4; Table 5) [8][9]. Serum lipase and amylase normalized. Clinically, the patient demonstrated progressive improvement across all organ systems:

Renal function recovered with creatinine trending toward baseline; urine output was restored; CRRT was subsequently discontinued.Respiratory status improved with progressive weaning of supplemental oxygen and resolution of ARDS-pattern changes.Neurological function recovered fully—encephalopathy resolved, patient is alert and oriented.Hemodynamic stability was maintained without vasopressor requirement.Abdominal distension and compartment physiology are resolved.

Follow-up imaging confirmed no further progression of pancreatic necrosis. No secondary pancreatic infection was identified during the admission. At discharge, outpatient follow-up was advised, including gastroenterology and lipid-focused review, strict dietary fat restriction, and ongoing monitoring for recurrence of hypertriglyceridemia or pancreatitis. Genetic evaluation for FCS was recommended as an outpatient priority if accessible.

Figure 4. Serial serum triglyceride trend during clinical course.

Serial triglyceride trend showing extreme hypertriglyceridemia (>14,000 mg/dL) at admission, persistent critical elevation during CRRT-supported medical therapy, a marked decline after the first TPE session (~3500 mg/dL), further reduction to approximately 300 mg/dL after the second session, and sustained control to <200 mg/dL by discharge. The post-TPE Session 1 intermediate value is a reconstructed estimate from the clinical course.

Table 5.Clinical timeline—day-by-day summary.

TG = triglycerides; PICU = pediatric intensive care unit.

This case exemplifies the catastrophic potential of extreme hypertriglyceridemia. Triglyceride levels exceeding 10,000 mg/dL, as observed here, are encountered almost exclusively in the context of genetic LPL pathway disorders, particularly FCS [4][9]. At such concentrations, the pancreatic microcirculation becomes saturated with chylomicrons, which are hydrolyzed by pancreatic lipase to generate high local concentrations of free fatty acids. These lipotoxic intermediates cause direct acinar cell necrosis, microvascular ischemia, and a self-amplifying inflammatory cascade [1][2].

The severity of organ dysfunction seen in our patient—AKI, ARDS, encephalopathy, and abdominal compartment syndrome—reflects the systemic toxicity of extreme lipemia. Prior published series confirm that triglyceride levels above 5000 mg/dL are associated with a substantially higher rate of severe and necrotizing disease, organ failure, and ICU admission [1][2][17].

We wish to explicitly acknowledge the diagnostic uncertainty inherent in this case. The label of ‘suspected FCS’ is used deliberately, as confirmatory genetic testing was not available during the index admission. Nevertheless, several clinical features strongly support this diagnosis: extreme chylomicronemia (>14,000 mg/dL) in a 14-year-old with no secondary causes; absence of diabetes, hypothyroidism, alcohol use, or relevant medications; and, crucially, failure to respond to LPL-dependent pharmacologic therapies (insulin, heparin) [4][5].

FCS must be distinguished from the more common polygenic or multifactorial hypertriglyceridemia, in which LPL activity is reduced but not absent. In multifactorial HTG, insulin and heparin can produce meaningful triglyceride reduction [11]. In true FCS, such treatments are futile. This distinction is not merely academic—it directly determines whether pharmacologic management can be expected to succeed, or whether plasma exchange must be considered the primary therapeutic strategy rather than the last resort [4][16].

Clinicians should maintain a high index of suspicion for FCS when triglycerides exceed 5000 - 10,000 mg/dL in a young patient without secondary causes, and when pharmacologic treatment fails to achieve triglyceride reduction within 12 - 24 hours [5][7]. Formal lipidology consultation and genetic testing should be arranged in all such cases, not only for acute management but also for long-term risk stratification and family screening [4].

CRRT served an essential and life-preserving role in this patient. The severe AKI, refractory metabolic acidosis, volume overload, and hemodynamic instability collectively created a physiologic milieu in which undertaking any further intervention, including TPE, would have been hazardous [10][13]. CRRT normalized the acid-base environment, restored hemodynamic stability, and corrected fluid balance, thereby creating the necessary physiologic platform for safe TPE delivery.

This concept of CRRT as a ‘bridge modality’ is an important framing for clinicians. In the context of HTG-AP, the goal of CRRT is not lipid clearance—it is organ support and metabolic rescue [13][14]. The persistence of critical hypertriglyceridemia on CRRT should not be interpreted as treatment failure; it should be interpreted as confirmation that a mechanistically distinct intervention is required.

Several prior reports have described the use of CRRT in severe pancreatitis-associated AKI and have documented its benefit in cytokine clearance and metabolic stabilization [13][14]. However, chylomicrons, with molecular weights in the billions of Daltons and particle diameters exceeding 80 nm, are physically incapable of passing through standard hemofilter membranes. Their clearance requires plasma removal, not filtration (Figure 5) [8][9].

Schematic diagram illustrating the mechanistic distinction between CRRT and TPE. Left panel: CRRT removes small-to-middle-molecular-weight solutes (urea, creatinine, electrolytes, cytokines) via diffusion and convection, correcting acid-base status, fluid balance, and uremic burden. Chylomicrons (CM; 80 - 1200 nm) are too large to pass through hemofilter membranes and are not removed. Right panel: TPE removes the entire plasma compartment, including chylomicrons, VLDL, and free fatty acids via plasma separation, replacing it with 5% albumin. This directly eliminates the lipotoxic substrate driving pancreatic and end-organ injury.

Figure 5. Mechanistic distinction between CRRT and TPE in HTG-AP.

The evidence base for TPE in severe HTG-AP, while predominantly retrospective and case-based, is consistent in demonstrating rapid and substantial triglyceride reduction [8][9][15][17]. Chen et al. reported triglyceride reductions of >80% per session in a cohort of patients with severe HTG-AP [8]. Gubensek et al. demonstrated clinical improvement and reduced organ failure scores following TPE [15]. Kremer Hovinga et al. performed a systematic literature review confirming the efficacy and relative safety of TPE in this indication [9].

The mechanism by which TPE produces clinical benefit extends beyond simple triglyceride removal. The exchange of patient plasma with albumin or FFP replenishes coagulation factors and functional LPL cofactors such as ApoC-II, potentially partially restoring LPL activity [8][15]. It also removes circulating inflammatory mediators, free fatty acids, and lipid peroxidation products, attenuating the systemic inflammatory response [9][17].

In our patient, the triglyceride reduction from >14,000 mg/dL at admission to approximately 3500 mg/dL after the first TPE session, 300 mg/dL after the second session, and <200 mg/dL at discharge was accompanied by normalization of pancreatic enzymes and progressive multi-organ recovery. While attribution of clinical recovery to TPE alone cannot be made with certainty in a single case—given the concurrent effects of CRRT, pharmacologic therapy, and intensive supportive care—the temporal correlation between TPE initiation and both biochemical and clinical improvement is strongly consistent with the published literature on TPE in severe HTG-AP [8][14][17].

A key conceptual contribution of this case is the explicit framing of CRRT and TPE as non-competing, sequentially complementary interventions in HTG-AP with multi-organ failure (Figure 6) [14]. Each modality addresses a distinct physiological domain: CRRT corrects the metabolic and renal consequences of critical illness, while TPE removes the primary offending pathological substrate. Neither modality alone would have been sufficient in this case.

Clinicians in resource-limited or low-volume settings may default to CRRT as the sole extracorporeal intervention when faced with severe pancreatitis and AKI, without recognizing the concurrent need for TPE. This case serves as a reminder that awareness of the therapeutic ceiling of CRRT—its inability to clear large lipoproteins—is essential for timely decision-making [13][14].

Figure 6. Treatment timeline—sequence and duration of key interventions.

Gantt-style treatment timeline illustrating the sequence and approximate duration of key interventions across the ICU admission. Pharmacologic therapy (insulin, heparin, fibrate, meropenem) was initiated on Day 1 and continued throughout. CRRT (CVVHDF on Baxter PrisMax) ran for approximately 48 hours (Days 1 - 4). TPE sessions were performed on Days 3 and 4. Vasopressor support was tapered and discontinued by Day 4 - 5. The patient was stepped down to ward care on Days 6 - 7 and discharged on Days 8 - 10.

Perhaps the most clinically instructive lesson of this case is the challenge of knowing when to escalate. In the acute phase, it is tempting to continue optimizing supportive care when the patient shows some improvement—particularly when pharmacologic lipid-lowering therapy and CRRT are producing measurable physiologic benefits. However, the persistence of triglycerides at dangerous levels despite 24 - 48 hours of maximal therapy should be recognized as a decisive indicator for TPE escalation [8][16].

Published guidance and case series suggest that when triglycerides fail to fall below 5000 mg/dL (or ideally 1000 - 2000 mg/dL) within 12 - 24 hours of pharmacologic therapy, particularly in cases where LPL deficiency is suspected, TPE should be initiated without further delay [9][15][16]. Delays in escalation risk compounding pancreatic necrosis, irreversible organ injury, and death.

Multidisciplinary coordination—between intensivists, nephrologists, apheresis specialists, and lipidologists—is essential for achieving timely TPE access in the ICU setting. Institutional protocols for this indication are warranted [16][18].

Several limitations of this report warrant explicit acknowledgment. First, the diagnosis of familial chylomicronemia syndrome was not genetically confirmed; the classification of ‘suspected FCS’ is based on clinical and biochemical criteria only, and multifactorial severe hypertriglyceridemia cannot be entirely excluded. Second, this is a single-patient case report, which precludes generalization of findings or causal inference. Third, several supportive data points—including exact serial triglyceride values between treatment phases, formal lipid subfractionation, ApoB levels, and serial creatinine and enzyme values at defined time points—were not available, limiting the precision of the reported treatment response. Fourth, the intermediate arterial blood gas values in Table 6 represent a clinically reconstructed trajectory rather than directly measured chart data and should be interpreted accordingly. Fifth, long-term follow-up data are limited; the patient’s lipid profile, recurrence risk, and response to dietary and pharmacologic management beyond discharge are not reported. Genetic evaluation and specialist lipidology follow-up were recommended, but outcomes are not yet known.

Table 6. Serial arterial blood gas trend.

Serial ABG values after admission are presented as a clinically reconstructed improvement trajectory based on the documented course of severe metabolic acidosis, CRRT-supported correction, and post-TPE recovery. Admission pH 7.10 and lactate 10 mmol/L were directly confirmed; intermediate values are included to reflect the physiologic trend.