DR RIKIN HASNANI

Pulmonary complication in

Pancreatitis

INTRODUCTION Acute pancreatitis is an acute

inflammatory process of the pancreas in its severe form, is complicated by the development of multi-organ dysfunction syndrome with a mortality of 15%-20%.

Amongst the systemic complications, pulmonary complications are the most frequent and potentially the most serious.

RANSON’S CRITERIA

If the score ≥ 3, severe pancreatitis likely.If the score < 3, severe pancreatitis is unlikely

PULMONARY COMPLICATIONS INCLUDE

Hypoxia Atelectasis Acute respiratory distress syndrome Pleural effusion

PATHOPHYSIOLOGY OF ACUTE PANCREATITIS

Acute pancreatitis evolves in three phases Initial phase is characterized by

intrapancreatic digestive enzyme activation and acinar cell injury which involves the first few hours of acute Pancreatitis.

The second phase characterized by an intrapancreatic inflammatory reaction and varying degrees of acinar cell necrosis, it evolves in approximately 12-72 h.

Finally, the third phase which involves the rest of the progression of Acute Pancreatitis is characterized by further progression of the pancreatic injury and the appearance of extrapancreatic changes including SIRS and ARDS.

It is during phase three that pulmonary insult occurs

Pulmonary complication are divided into three stages

Stage 1: Hypoxemia with no radiological abnormalities

Stage 2 : Hypoxemia with radiological abnormalities

Stage 3 : ARDS

STAGE 1: HYPOXEMIA WITH NO RADIOLOGICAL ABNORMALITIES

Tachypnea, mild respiratory alkalosis, and hypoxemia are seen in almost two thirds of patients with Acute Pancreatitis during the first 2d of admission to the hospital.

In these patients, physical examination is essentially normal, chest radiographs rarely demonstrate abnormalities.

Imrie and co-workers showed that 45% of patients have severe arterial hypoxemia (PaO2 < 60mmHg) and indicated that a PaO2 of < 52.5 mmHg is associated with a mortality of more than 30%.

The major cause of hypoxia is ventilation and perfusion mismatch which results in a right to left intrapulmonary shunting of up to 30% of cardiac output.

In two studies, Imrie and coworkers correlated the overall mortality with the degree of hypoxemia. They found that patients with arterial pO2 below 70 mmHg have a mortality of 3% to 5.9% and when the arterial pO2 decreases below 60 mmHg the mortality rate increases to about 14%.

STAGE 2 : HYPOXEMIA WITH RADIOLOGICAL ABNORMALITIES

Radiological abnormalities seen are 1- Pleural effusion(4%-17%) 2- Atelactasis or Pulmonary infiltrates

(15%) 3- Pulmonary Edema(8%-50%)

PLEURAL EFFUSION Presence of pleural effusion is currently

considered an indication of severe pancreatitis and not just a marker of the disease.

The pleural effusions are Left sided in 68% , Bilateral in 22% , Right-sided in 10%, of cases.

PATHOPHYSIOLOGY OF PL. EFFUSION IN AC. PANCREATITIS Various pathogenic mechanisms have been proposed to

explain the development of pleural effusions associated with acute pancreatitis:

(1) increased permeability of lymphatics and fluid leak caused by pancreatic enzymes that may diffuse from the peritoneal side to the thoracic side of the diaphragm,

(2) impaired lymphatic drainage of pleural exudate caused by obstruction of lymphatic vessels by the high enzymatic content of the pleural fluid, and

(3) increased permeability of diaphragmatic capillaries caused by the inflammatory process in the adjacent pancreas.

CLINICAL FEATURES In patients with pleural effusion

associated with acute pancreatitis, symptoms are primarily abdominal (pain,nausea and vomiting);

occasionally, respiratory symptoms(pleuritic pain and dyspnea) may also be present.

Pleural effusions in Acute Pancreatitis are usually small, occasionally hemorrhagic , and

are characterized by High amylase (up to 30 times greater than

corresponding serum value, usually >1000 IU/l) Protein (> 30 gm/L), Fluid LDH / serum LDH > 0.6 . WBC count vary from 1,000 to 50,000

cells/mm3.

MANAGEMENT Pleural effusions associated with acute

pancreatitis usually are self-limited and resolve when the pancreatic inflammation decreases without requiring therapeutic drainage.

If the pleural effusion does not resolve within 2 weeks after treatment for the pancreatic disease, the possibility of a pancreatic abscess or a pseudocyst should be considered.

CHRONIC EFFUSIONS Chronic pleural effusions are usually

associated with chronic relapsing pancreatitis and pancreatic pseudocyst.

Chronic effusions are large, may occupy the entire hemithorax,and reaccumulate rapidly after thoracentesis.

Mechanism of chronic effusion is a pancreaticopleural fistula, a direct communication between the pancreas and the pleural space

Pt with chronic effusion presents with respiratory symptoms – dyspnoea, chest pain with minimal or no abdominal symptoms.

Patients with chronic pancreatic pleural effusions should be treated initially with nasogastric tube placement, no oral intake, parenteral nutrition, and repeated therapeutic thoracenteses.

Inhibition of pancreatic secretion with octreotide has been shown to be useful in promoting the closure of pancreaticopleural fistulas in some cases.

Surgery is indicated if pleural fluid continues to accumulate after 2-3 weeks of medical therapy.

ATELACTASIS Consolidation of lung tissue and

atelectasis are frequent radiological observations.

Atelactasis is due to a decrease in the production of pulmonary surfactant and diaphragm muscle dysfunction.

IL-1 and TNF-α plays avital role in diaphragm muscle dysfunction.

ARDS Of the patients who develop Acute

pancreatitis , 15% to 20% develop ARDS with an associated mortality of 56%.

ARDS usually manifests itself between two to seven days following the onset of Acute pancreatitis, but may have a much more rapid course.

ARDS accounts for 50%-90% of all deaths from pancreatitis

Clinical features include severe dyspnea and extreme hypoxemia refractory to a high inspired oxygen concentration.

Multilobar pulmonary infiltrates in patients with previous normal radiographs and a relatively normal pulmonary capillary wedge pressure (< 18 mmHg) are noted.

PaO2/FiO2 is usually <200

PATHOPHYSIOLOGY OF ARDS IN PANCREATITIS

The pathophysiology of ARDS in Acute pancreatitis is poorly understood.

Actions of pancreatic enzymes as well as inflammatory mediators released as a result of pancreatic injury play a key role in the pulmonary complications.

INFLAMMATORY MEDIATORS IN RESPIRATORY INSUFFICIENCY 1 Phospholipase A2 2 Trypsin 3 FFA/Lipoprotein lipase 4 Complement activation (C5a) 5 MIF 6 IL-6, IL-8, IL-1β 7 NO 8 TNF-α 9 ICAM-1 10 β-2-integrin (CD11b/CD18) 11 Trypsin 12 NF-κB 13 Substance P

Activated trypsin: It is a possible source for the cause of pulmonary insufficiency. Trypsin causes damage to the pulmonary vasculature and increases endothelial permeability

Trypsin is capable of activating different complement factors directly, which can stimulate cytolysis and chemotactic leukocytes.

Phospholipase A :PLA2, which is activated by trypsin in the duodenum, is known for its ability to remove fatty acids from phospholipids.

The basic reason for pulmonary insufficiency and ARDS in Acute pancreatitis is due to the destruction of the surfactant.

One of the main components of surfactant is phospholipid - dipalmitoylphosphatidylcholine, which is a perfect substrate for PLA2.

Büchler et al showed that there is a strong correlation between serum-activated PLA2 and pulmonary insufficiency.

In their prospective study, patients with pulmonary failure demonstrated a notably higher catalytic PLA2 activity during the first week of Acute pancreatitis than patients without arterial hypoxemia.

They also showed that it was isotype II of PLA2 which is more specific to pulmonary involvement.

Platelet activating factor:PAF stimulates PMN white cells and regulates the interaction between PMN cells and endothelial cells, facilitating migration of activated white cells into tissue spaces. PAF is a structural component of membrane lipids and is released upon the action of PLA2

Free fatty acid:The free fatty acids released from triglycerides (TG), have been shown to damage capillary alveolar wall membranes.

TNF-α:TNF-α activates neutrophils and increases lung damage levels at higher concentration in the lung.

Role of other substances like IL 8, IL10,NO, Macrophage migration inhibitory factor,in Acute pancreatitis are being studied.

MANAGEMET OF ACUTE PANCREATITIS

NPO Fluid Resuscitation Octreotide 100-200mcg /sc/tid Management of oxygenation NIV or MV Management of Metabolic

complications Lexipafant – PAF antagonist in stage 3

trials decreases mortality if used at onset of disease.

Emerging drugs: CCK receptor antagonist: loxiglumide Prostaglandins: PGE1

Platelet activating factor (PAF) antagonist TNF monoclonal antibody: Infliximab

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