2. Ramesh Kumar, 45 yrs. Male History of RTA Diagnosis – Fracture Supracondylar Femur Right with Compound Fracture both Bone Leg Left. Vitals on admission Heart Rate - 88/pm, B.P. – 106/76, R.R. – 17/pm

3. ACUTE RESPIRATORY DISTRESS SYNDROME Acute respiratory distress syndrome (ARDS) is a clinical syndrome of severe dyspnea of rapid onset, hypoxemia, and diffuse pulmonary infiltrates leading to respiratory failure. Acute lung injury (ALI) is a less severe disorder but has the potential to evolve into ARDS. ARDS is characterized by – 1. Tachypnea & cyanosis refractive to oxygen therapy. 2. Markedly reduced lung compliance. 3. Diffuse alveolar shadowing on Chest X-Ray. 4. Pulmonary odema, congestion & Hyaline membrane on histological examination. The first detailed clinicopathological description of ARDS was provided by Ashbaugh and colleagues. The annual incidences of ALI and ARDS are estimated to be 30/ 100,000 and 10/100,000, respectively.

4. Etiology : Clinical Disorders Commonly Associated with ARDS Direct Lung Injury Indirect Lung Injury Pneumonia Sepsis Aspiration of gastric contents Severe trauma Pulmonary contusion Multiple bone fractures Near drowning Flail chest Toxic inhalation injury Head trauma Burns Multiple transfusions Drug overdose Pancreatitis Post-cardiopulmonary bypass The most common causes of ALI/ ARDS are sepsis, pneumonia, aspiration of gastric contents, and multiple trauma.

5. Pathophysiology : The natural history of ARDS is marked by three phases – exudative, proliferative, and fibrotic – each with characteristic clinical and pathologic features. Exudative Proliferative Fibrotic Hyaline Interstitial Inflammation Fibrosis Membranes Interstitial Fibrosis Edema Day : 0 2 7 14 21 ...

6. Exudative Phase : In this phase, alveolar capillary endothelial cells and type I pneumocytes. (alveolar epithelial cells) are injured leading to the loss of the normally tight alveolar barrier to fluid and macromolecules. Edema fluid that is rich in protein accumulates in the interstitial and alveolar spaces. Alveolar edema dependent portions of the lung  Collapse of the dependent lung  decrease lung compliance  intrapulmonary shunting and hyproxemia  increase work of breathing  dyspnea.

7. Proliferative Phase : This phase of ARDS usually lass from day 7 to day 21. Most patients recover rapidly and are liberated from mechanical ventilation during this phase. Histologically, the first signs of resolution are often evident in this phase with the initiation of lung repair, organization of alveolar exudates, and a shift from a neutrophil to a lymphocyte-predominant pulmonary infiltrate. As part of the reparative process, there is a proliferation of type II pneumocytes along alveolar basement membranes. These specialized epithelial cells synthesize new pulmonary surfactant and differentiate into type I pneumocytes.

8. Fibrotic Phase : Histologically, the alveolar edema and inflammatory exudates of earlier phases are now converted to extensive ductal and interstitial fibrosis. Acinar architecture is markedly distrupted, leading to emphysema-like changes with large bullae. Intimal fibroproliferation in the pulmonary microcirculation leads to progressive vascular occlusion and pulmonary hypertension. The physiologic consequences include an increased risk of pneumothorax, reductions in lung compliance, and increased pulmonary dead space.

9. CLINICAL FEATURES : The patient develops progressive dyspnea and often non productive cough usually hours or days after a recognized predisposed condition. Acute onset progressive Dyspnea Non Productive cough Techypnea Cyanosis Refractive to oxygen therapy Hypoxia Agitation Respiratory Failure DIAGNOSIS : Because the early features of ARDS are nonspecific high degree of suspicion is necessary to make a diagnosis. In the majority of patients, the initial diagnosis of ALI/ARDS is made clinically. Invasive techniques for diagnosis are of limited clinical utility.

10. DIAGNOSTIC CRITERIA FOR ALI AND ARDS AMERICAN EUROPEAN CONSENSUS CONFERENCE DEFINITION OF ALI & ARDS. Oxygenation Onset Chest Radiograph Absence of Left Atrial Hypertension ALI : Acute Bilateral alveolar PCWP < 18 mmHg or no Pao2/FIo2 < or interstitial clinical evidence of 300 mmHg infiltrates increased left atrial ARDS : pressure Pao2/Flo2 < 200 mmHg Note : ALI acute lung injury, PAO2 arterial partial pressure of O2, FIO2 inspired O2 percentage, PCWP pulmonary capillary wedge pressure.

11. INVESTIGATIONS : 1. Chest X-ray : Chest radiograph in early stages are usually normal. Chest X-ray in the initial stages reveals aleveolar & interstitial opacities involving at least ¾ of the lung. These characteristics are not specific for ARDS but can be indinguishable for the cardiogenic pulmonary edema. Unlike latter however the chest x-ray in ARDS rarely shows cardiomegaly, pleural effusion or pulmonary vascular redistribution.

12. 2. Arterial Blood Gases : In the initial stages ABG analysis shows decreased PCO2 and decreased PAO2 and alkalosis. In the latest stages there is increased PCO2 and decreased PAO2 and acidosis. Ultimately leading to respiratory failure. 3. ECG : ECG study is essential to rule out any cardiac abnormality. 4. Echo Cardiography : Echo Cardiography study is normal unless there is some cardiac disease. 5. CT Scan : CT Scan shows the extensive hetrogenity.

13. TREATMENT : - The recognition and treatment of the underlying medical and surgical disorders (e.g. sepsis, aspiration, trauma); - Prophylaxis against venous thromboembolism, gastrointestinal bleeding, and central venous catheter infections; - The prompt recognition of nosocomial infections and their treatment. - Provision of adequate nutrition. - Fluid and Hemodynamic Management :- A reasonable strategy is to aim to achieve the lowest intravascular volume that maintains adequate tissue perfusion as measured by urine output or other organ perfusion and metabolic acid base status. If organ perfusion cannot be maintained in the setting of adequate intravascular volume, maintained in the setting of adequate Intravascular volume, then administration of vasopressors and/ or inotropes should be used to restore end-organ perfusion.

14. - Glucocorticoids : Current evidence does not support their use in the care of and ARDS patients. One the other hand, if patients fail to improve after 1 week of supportive therapy and have no contraindications to glucocorticoid therapy, providers may wish to consider an empirical trial of them in an attempt to speed ARDS resolution. There is no data regarding the preference of one steroid over the other. - Management of Mechanical Ventilation :- Ventilation in volume control mode with a tidal volume of 6 mL/kg predicted body weight plateau pressure less than 30 cm H 2 O has been shown to improve mortality in ALI/ARDS compared with a larger tidal volume (12 mL/kg.). This improvement in survival using the low tidal volume (6ml/kg) represents the most substantial benefit in ARDS mortality demonstrated for any therapeutic intervention in ARDS to date.

15. A STEPWISE APPROACH TO MECHANICAL VENTILATION IN ARDS 1. Calculate predicted body weight (PBW) in Kilogram Men = 50 + 5.42 [height (cm) – 60] Women = 45.5 + 5.42 [height (cm) – 60] 2. Ventilator mode Volume cycle, assist control 3. Tidal volume (V T ) Initial V T 8 mL/kg PBW Reduce to 6 mL/kg over 2 – 4 h if ventilation adequate Goal inspiratory plateau pressures < 30 cmH 2 O; reduce V T to as low as 4 mL/kg as needed (and permitted by ventilation) to achieve this goal. 4. Oxygenation Pao goal = 55 – 80 mmHg or pulse oximetry oxygen saturation 88 – 95% Use the minimal amount of PEEP to keepFIo 2 < 0.6 and meet Pao 2 goal. 5. Respiratory rate and acidosis management Goal arterial pH = 7.30 – 7.40 If pH < 7.30, increase respiratory rate up to 35 breaths/ min. If pH < 7.30 and respiratory rate = 35, consider starting intravenous bicarbonate (or equivalent buffer).

16. If the above strategy fails and the patient is suffering from persistent hypoxemic respiratory failure, consider the following : 1. Neuromuscular blocking agents (if not already in use) 2. Prone position ventilation 3. Recruitment maneuvers 4. Inverse ratio ventilation, nitric oxide, high- frequency ventilation, extra corporeal membrane oxygenation, or partial liquid ventilation as part of a clinical research trial.

17. PROGNOSIS : Mortality – Recent mortality estimates for ARDS range from 41 to 65%. Mortality in a ARDS is largely attributable to nonpulmonary causes, with sepsis and nonpulmonary organ failure accounting for >80% of deaths. Risk Factors for mortality : Several risk factors for mortality to help estimate the prognosis have been identified. Major risk factor for ARDS mortality are non-pulmonary. 1. Advanced age > 75 years. 2. Sepsis 3. Chronic liver disease 4. Chronic alcohol abuse 5. Chronic immunosupression 6. Chronic renal disease 7. Non pulmonary organ failure.

18. Pre-existing organ dysfunction from chronic medical illness is an important additional risk factor for increased mortality. Patient with ARDS from direct lung injury (Pneumonia, Pulmonary Contusion & Aspiration) have nearly twice the mortality of those with the indirect causes of lung injury, while surgical & trauma patient with ARDS especially those without direct lung injury have a better survival rate.

19. COMPLICATIONS : Complications are common in any critically in patients. 1. Pulmonary embolism 2. Myocardial infarction 3. GI Bleedings 4. Barotrauma : Barotrauma occurs when air dissects out of the air ways or alveolar space into surrounding tissues, leading to pneumothorax, pneumomediastinum, pneumatocele, or sub-cutaneous emphysema. Treatment of barotrauma depends on the location of the extravasated air. Pneumothorax should be considered in any mechanically ventilated patients of ARDS who develops sudden, unexplaned hypoxemia, respiratory distress, or hemodynamic instability. A chest radiograph (preferably upright) is usually sufficient to make the diagnosis, but in many cases there may not be time to obtain one and immediate thoracostomy is essential to save life.

21. 6. Multiorgan System Dysfunction : Although ALI and ARDS are often thought of as primary pulmonary disorders, evidence is accumulating to suggest that they are systemic disorders with many similarities to sepsis or SIRS. Multiorgan system dysfunction is a common complication in ALI/ARDS, Organ dysfunction may result from the underlying cause of ALI/ARDS, such as sepsis, or occur independently.

22. 7. Neuromuscular Weakness : Patient of ARDS are at high risk for developing the neuromuscular weakness that persists after resoulation of ARDS and can complicate weaning from the mechanical ventilation and rehabilitation. These clinical syndromes are commonly called critical illness polyneuropathy but actually have components of neuropathy and myopathy that can coexist or occur separately. Prolonged muscle weakness is most common in critically ill patients who are treated with glucocorticoids. In the absence of compelling clinical indication such as underlying connective tissue disease the use of glucocorticoid should not be routine. FUNCTIONAL RECOVERY IN ARDS SURVIVORS : Majority of patients of ARDS survivors recover nearly normal lung function. Patients usually recover their maximum lung function within 6 months.

23. FAT EMBOLISM SYNDROME Fat embolism syndrome (FES) is a clinical entity first described over 150 years ago by Bergmann. It is very important to differentiate FES, a complex with potentially catastrophic cardiopulmonary and cerebral dysfunction, from fat embolization, a far more common and often subclinical entity. Incidence of fat embolism in polytrauma patients is 90%. Incident of the FES is 1 – 3% in the patients with a single major fracture.

24. Causes : Fractures of the long bone. Pelvic Trauma, Intramedullary nailing of long-bone fractures, Hip arthroplasty, and knee arthroplasty. Sickle cell disease, Acute pancreatitis Decompression sickness Total parenteral nutrition. Most common cause of FES is fractures of the long bones. Intramedullary orthopedic surgeries are the most common iatrogenic cause of FES.

25. PATHOPHYSIOLOGY : In the initial phase, fat and marrow are displaced from the bones, enter the venous system, and travel through the heart to enter the lungs. There the emboli may cause shunting, severe hypoxemia, and right ventricular dysfunction. The secondary phase may involve inflammatory mediators responsible for the interstitial edema or acute respiratory distress syndrome that may ensue. CLINICAL FEATURES : The principal clinical features of fat embolism syndrome are:  Respiratory Failure  Cerebral dysfunction  Petechiae

26. FES is most common after the 24-72 hrs. of the inciting cause

27. Fat embolism syndrome : above with clinical pattern of symptoms/signs; 24-72 hrs after insult: - Petechial Rash - head, neck, anterior thorax, subconjunctiva, axillae – 20-50% of cases - Respiratory – tachypnea, dyspnea, b/l crackles, hemoptysis, bilateral infiltrates, ARDS - Neurological signs – confusion, drowsiness, coma – may resolve - Fever - Cardiovascular: tachycardia, hypotension - Retinal changes (fat or petechiae - Purtscher’s retinopathy) - Jaundice - Renal (anuria or oliguria) - Hematological o Thrombocytopenia (>50% decrease) o Anemia (>20% decrease) o ESR >71 mm/h

28. DIAGNOSIS : The diagnosis of FES remains one of exclusion. A number of authors have suggested clinical criteria for diagnosing FES. Gurd’s Criteria for the diagnosis of FES Table-I : Gurd's Criteria Major Criteria Petechial rash (One necessary for diagnosis) Respiratory insufficiency Cerebral involvement Minor Criteria (One necessary for diagnosis) Tachycardia > 120 beats/ min Fever > 39.4°C Retinal signs – fat or petechiae Jaundice Renal signs – anuria or oliguria Laboratory Findings Thrombocytopenia (One necessary for diagnosis) Anemia High ESR Fat macroglobulinemia

29. FES Doesn't occur before 12 Hrs. and after 2 weeks of the inciting cause. Table-II : Schonfeld's Criteria Petechiae 5 Chest X-ray changes 4 (Diffuse alveolar infiltrates) Hypoxemia (PaO2 <9.3 kPa) 3 Fever (<38°C) 1 Tachycardia (>120 beats/ min) 1 Tachypnea (>30 breaths/ min) 1 Confusion 1 Cumulative score > 5 required for diagnosis

30. LABORATORY STUDIES There is no pathognomic test during the course of a Fat Embolic Syndrome, but a high index of suspicion is helpful in diagnosis. Close observations should be kept for the clinical signs and symptoms of Fat Embolic Syndrome on any patient at risk. However, some investigations can be helpful in conjunction with the clinical features. 1. ABGs ABGs may show a low PaO 2 and PaCO 2 with a respiratory alkalosis in the early stages but in later stages hypoxemia and hypercapnia with respiratory acidosis may be prominent feature due to diffusion defects.

31. 2. Urine and Sputum Examination. Samples may contain fat globules but these tests are non-specific. 3. Haemotological Tests. During the acute phase of Fat Embolic Syndrome, there may be increase in FDPs, positive D-Dimer test, thrombocytopenia and other coagulation abnormalities. Patients often have a mild anemia. 4. Biochemical tests Liver and renal function tests should performed. Serum electrolytes are mandatory. Hypocalcemia may be present due to saponification of the circulating unbound free fatty acids.

32. IMAGING STUDIES : 1. X-ray chest The classical chest x-ray of fat embolism syndrome shows multiple flocculent shadows (snow storm appearance) . However, the spectrum includes a diffuse, ground glass appearance or military dissemination of very fine shadows. Later, the picture may be complicated by infection or pulmonary edema. 2. Echocardiography Transesophageal echocardiography has been used to detect fat embolism in patients who are undergoing invasive intramedullary procedures.

33. 3. CT Scan Brain. CT Scan brain (plain) may be normal or may reveal diffuse white-matter petechial haemorrhages consistent with microvasvular injury. 4. Spiral CT Scan chest. Helical CT Scan chest may be normal as the fat droplets are lodged in capillary beds. Parenchymal changes consistent with lung contusion. Acute lung injury, or ARDS may be evident. 5. MRI Scant data exist regarding MRI findings in patients with fat embolic syndrome.

34. TREATMENT : Mainstay of treatment in supportive. - Cardiovascular therapy including maintaining adequate preload and positive inotropy is necessary to preserve cardiac output. - For hypoxemia 100% oxygen via an endotracheal tube. - Other therapeutic regimens used after the development of FES including heparinization, dextran, and parenteral ethanol cannot be recommended. - Prophylactic corticosteroid therapy may minimize the incidence of FES. - If possible, it is best to delay all but emergency surgery in trauma patients who develop FES until the syndrome has progressed to its full severity and stabilized or improved. - An exception is the patient who requires fixation of fractures to halt continuing fat embolization.

35. Deterrence/Prevention:  Early immobilisation of fractures seems to be the most effective way of reducing the incidence of this condition.  Corticosteroids as prophylaxis for fat embolism syndrome  Several studies have demonstrated varying results using corticosteroids, usually methylprednisolone, in patients identified as being at high risk for the syndrome.  Although the data appear compelling, the optimal timing, duration, and dose of steroids are undetermined.

36. PROGNOSIS : The mortality rate from fat embolism syndrome is 5 to 15%. Even severe respiratory failure associated with fat embolism seldom leads to death. The prognosis is worse in older patients and those with more severe injury but is not affected by gender. Results of Randomized Controlled Trials of Corticosteroids in the Prevention of Fat Embolism Syndrome Dose Model Timing Duration of Study Effect on Disease Incidence 30 mg/kg Dog Pre-event 60 min None 10 mg/kg q8h for 24 h Human trauma At admission No data Declining 7.5 mg/kg q6h for 12 h or placebo Human trauma Within 12 h 2 d Declining

37. MEDICAL/LEGAL PITFALLS:  Assuming altered mental status, fever, and hypoxia are due to fat embolism, the lack of a search for treatable or life-threatening disorders before making the diagnosis may lead to litigation if such a disorder is discovered later.  CT scan of the head is necessary to rule out intracranial pathology.  A careful search for infectious agents and possibly the institution of empiric antibiotics are necessary until an infectious source is ruled out.  Judicious use of crystalloids, colloids, and diuretics is necessary; volume depletion may precipitate shock and organ dysfunction, but volume overload may worsen the hypoxia.

38. EFFECT OF INTRAMEDULLARY NAILING : Fat embolism due to IM nailing was discribed by Kuntscher. He recommended the avoidance of nailing after trauma in cases with severe injuries or when fat embolism was already present. The incidence of fat embolism depends on which bone is involved most commonly with the femur.

39. In randomised clinical study unreamed nailing was associated with a lower rate of pulmonary complications but differences was not statistically significant. IM instrumentation  Rise of IM pressure  Liberation of bone marrow contents in blood  Bone marrow contents in Lungs  Increase pulmonary arterial pressure  Decreased oxygenation & ARDS

40. TIMING OF FRACTURE FIXATION IN POLYTRAUMA PATIENTS : In multiple injured patients with two sever injuries benefits of IM nailing of femoral fractures in 1 st 48 hours is well established. But this should be avoided in patients who are at the risk for SIRS and organ dysfunction which include the patients with shock & sever pulmonary injuries and selected patients of sever CNS trauma when it is determined that surgery may lead to hypoxia and hypotension, that would extend the primary brain injury. Early temporary fixation is done with the external fixator in these cases to decrease the immune system stimulation leading to the SIRS. Conversion from the external fixator to the nailing is done after 4 days this duration is appropriate to allow for the reduction in inflammatory response to the initial injury.

41. BIBLIOGRAPHY 1. Harrison's – Principles of Internal Medicine . 2. Crouftan and Douglas – Text Book of Respiratory Medicine. 3. Wylie's – Text Book of Anesthesia. 4. Fink's – Principles of Critical Care.

42. Thanks