Fat Embolism Syndrome (FES)

Fat Embolism Syndrome (FES)

➧ Fat embolism can be difficult to diagnose. It most often follows a closed fracture of a long bone but there are many other causes.

Epidemiology:

➧ Incidence of this complication ranges from 0.5 to 11% in different studies. It varies considerably according to the cause. Patients with fractures involving the middle and proximal parts of the femoral shaft are more likely to experience fat embolism. Age also seems to be a factor with young men at the highest risk.

Etiology:

1-Fractures: Closed fractures produce more emboli than open fractures. Long bones, pelvis, and ribs cause more emboli. Sternum and clavicle cause less. Multiple fractures produce more emboli.

2- Orthopedic Procedures: Intramedullary nailing of long bones, Fixation of cemented hip prosthesis.

3-Massive soft tissue injury

4-Severe burns

5-Liposuction

6-Bone marrow biopsy

7-Bone marrow harvesting and transplant

8-Cardio-pulmonary bypass

9-Non-traumatic settings occasionally lead to fat embolism. These include conditions associated with: 

-Fatty liver

-Acute pancreatitis

-DM

-Osteomyelitis

-Bone tumor Lysis

-Pathological fractures

-Sickle cell crisis (causing bone infarcts)

-Decompression sickness

-Prolonged corticosteroids therapy

-Cyclosporine A solvent

-Parenteral lipid infusion

Sevitt’s classification:

1-Subclinical (Incomplete) form: Fat emboli present in blood and lungs, no symptoms/signs

2-Non-fulminant (Classic) form: Pulmonary dysfunction, cerebral dysfunction, petechiae

3-Fulminant form: Rare, rapid onset (within hours) of acute cor-pulmonale, respiratory failure, coma, and death.

Principal clinical features (triad) of FES:

1-Respiratory failure (dyspnea and hypoxia)

2-Cerebral dysfunction (confusion)

3-Petechiae

➧ Clinical features usually present between 24-72 h. after trauma (lucid interval). This is especially after fractures, when fat droplets act as emboli, becoming impacted in the pulmonary microvasculature and other microvascular beds, especially in the brain.

➧ Embolism begins rather slowly and attains a maximum in about 48 h.

➧ The initial symptoms are probably caused by mechanical occlusion of multiple blood vessels with fat globules that are too large to pass through the capillaries.

➧ The vascular occlusion in fat embolism is often temporary or incomplete as fat globules do not completely obstruct capillary blood flow because of their fluidity and deformability.

➧ The late presentation is thought to be a result of hydrolysis of the fat to more irritating free fatty acids which then migrate to other organs via the systemic circulation.

➧ It has also been suggested that paradoxical embolism occurs from shunting.

Clinical Presentation:

➧ There is usually a latent period of 24-72 h. between injury and onset.

➧ Symptoms: There is vague pain in the chest and shortness of breath.

➧ Signs: The onset is sudden, with:

-Restlessness

-Fever occurs, often at more than 38.3° C with a disproportionate tachycardia.

-Drowsiness with oliguria is almost pathognomonic.

➧ CNS signs: including a change in the level of consciousness, are common. They are usually non-specific and have the features of diffuse encephalopathy with acute confusion, stupor, coma, rigidity, or convulsions. Cerebral edema contributes to neurological deterioration.

Diagnostic Criteria:

A) Gurd's and Wilson’s Criteria:

-Diagnosis requires at least one sign from the major criteria and at least four signs from the minor criteria. (Table 1)

Table 1: Gurd's and Wilson’s Criteria

B) Schönfeld’s Criteria:

-Diagnosis requires a score of more than 5. (Table 2)

Table 2: Schönfeld’s Criteria

C) The clinical diagnosis is assured if all three of the following criteria are present within 72 h. after traumatic fracture:

1-Unexplained dyspnea, tachypnea, arterial hypoxia with cyanosis, and diffuse alveolar infiltrates on chest X-ray.

2-Unexplained signs of cerebral dysfunction, such as confusion, delirium, or coma.

3-Petechiae over the upper half of the body, conjunctiva, oral mucosa, and retina.

Differential Diagnosis:

➧ Dyspnea, hypoxia, and abnormal CXR: can occur with thrombo-embolism and pneumonia.

➧ Cerebral dysfunction: can occur with hypoxia or meningitis but the rash of meningococcal septicemia is all over and spreads rapidly. It can also occur as a late feature of head injury.

➧ Thrombotic Thrombocytopenic Purpura (TTP).

Investigations:

CBC: 

-Hematocrit: is decreased, occurs within 24-48 h., and is due to intra-alveolar hemorrhage. 

-Platelets: are decreased.

Serum Lipase: is increased, but this is not pathognomonic as it occurs in any bone trauma.

Serum Calcium: is decreased.

Cytological Examination: urine, blood, and sputum may detect fat globules that are either free or in macrophages. This test has low sensitivity and a negative result does not exclude fat embolism. 

Arterial Blood Gases: will show hypoxia, PaO₂ usually less than 60 mmHg, and hypocapnia. Continuous pulse oximeter monitoring may enable hypoxia from fat embolism to be detected in at-risk patients before it is clinically apparent.

ECG: Ischemia, Rt. Ventricular strain, Rt. Axis deviation, RBBB, Arrhythmia.

Chest X-ray: may show evenly distributed, fleck-like pulmonary shadows (Snow Storm appearance), increased pulmonary markings, and dilatation of the right side of the heart.

CT Head: (to rule out intracranial pathology).

CT Chest: (to rule out chest pathology).

Management:

A) Supportive

1-Ensuring good arterial oxygenation: High flow rate of oxygen is given to maintain the arterial oxygen tension in the normal range.

2-Restriction of fluid intake and Diuretics: to minimize fluid accumulation in the lungs so long as circulation is maintained.

3-Maintenance of intravascular volume: is important because shock can exacerbate the lung injury caused by FES. Albumin has been recommended for volume resuscitation in addition to the balanced electrolyte solution, because it not only restores blood volume but also binds fatty acids, and may decrease the extent of lung injury.

4-Mechanical ventilation (APRV) and Positive End-Expiratory Pressure (PEEP): may be required to maintain arterial oxygenation.

B) Pharmacological

1-Corticosteroids: Methylprednisolone (membrane stabilizer, decreases endothelial damage caused by free fatty acids).

2-Low dose heparin: 2500 u / 6 h. (reduce the degree of pulmonary comprise and intravascular coagulation despite the risk of hemorrhage and intravascular lipolysis).

3-Dextran-40: (decreases intravascular thrombosis when ESR is elevated).

4-Ethanol: (decreases lipolysis)

5-Dextrose: (decreases free fatty acid mobilization)

6-DVT prophylaxis

7-Nutrition

C) Surgical:

1-Prompt surgical stabilization of long bone fractures within 24 h. reduces the risk of the syndrome.

2-Use of vacuum or venting during reaming of long bones.

3-Prophylactic IVC filter in at-risk patients.

Prognosis:

➧ The mortality rate from FES is 5-15%. 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.

➧ Criteria of bad prognosis: Sevitt’s class, Serum lipase, Lipuria, ARDS.

Prevention:

➧ Early immobilization of fractures seems to be the most effective way of reducing the incidence of this condition.

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Porphyric Crisis

Porphyric Crisis (Acute Neurovisceral Crisis) 

Background: 

-The porphyrias are caused by enzyme deficiencies in the heme production pathway. Such deficiencies may be due to inborn errors of metabolism or exposure to environmental toxins or infectious agents.

-The disease was named porphyria due to the red discoloration of urine in affected patients, (Figure 1).

-Crises are four to five times more common in women and usually occur in their early 30s.

Figure 1: Porphyria Red Urine

Triggering factors: 

Enzyme-inducing drugs: 

-Barbiturates (Thiopental, Methohexital), Etomidate, Enflurane, Alcuronium, Mepivacaine, Pentazocine, Nifedipine, Verapamil, Diltiazem, Phenytoin, Hydralazine, Phenoxybenzamine, Aminophylline 

Physiological: 

-Menstruation, Fasting, Dehydration, Stress, Infection, Anemia, Endogenous hormones 

Habits: 

-Smoking, Alcohol 

Clinical Picture: 

CNS: 

-Autonomic neuropathy (Fever, Pain, Constipation, Gastroparesis, Postural hypotension) 

-Peripheral neuropathy (Skeletal muscle weakness, Quadriparesis, Bulbar palsy, Respiratory failure) 

-Cranial nerve palsy 

-Seizures 

-Psychiatric features (Mood disturbance, Confusion, Psychosis) 

CVS: 

-Tachycardia, Hypertension 

GIT: 

Acute abdominal pain, Vomiting, Diarrhea, Dehydration, Electrolyte disturbance (↓ [Na⁺, K⁺, Mg⁺²]) 

Management: 

Remove triggering factors (above) 

Specific R: 

-Hematin, Heme arginate / Heme albumin, Somatostatin, Plasmapheresis 

Symptomatic R: 

-Pain: Substantial doses of Opioids 

-Nausea and Vomiting: Prochlorperazine, Ondansetron 

-Anxiety: Lorazepam, Midazolam in low doses 

-Insomnia: Zopiclone 

-Delirium: Haloperidol 

-Tachycardia & Hypertension: β-adrenergic blocking agents, Glyceryl trinitrate 

-Seizures: Benzodiazepines, Levetiracetam, Clonazepam, Gabapentin, Vigabatrin, Magnesium sulphate 

-Sedation: Propofol, Alfentanil infusions. The clinical safety of prolonged midazolam infusion is unknown. 

-Thromboembolic prophylaxis: LMW heparins 

-Stress ulcer prevention: IV Omeprazole, Ranitidine 

-Correction of electrolytes

Mechanical Ventilation for Respiratory failure

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Treacher Collins Syndrome

Treacher Collins Syndrome:

-A craniofacial defect associated with developmental anomalies of the first arch. 

-Abnormalities vary from minimal, to complete syndrome. 

-The syndrome is named after Edward Treacher Collins, an English surgeon and ophthalmologist, who described its essential traits in 1900. 

-Patients may require anesthesia for maneuvers to improve upper airway obstruction temporarily, or for correction of some of the congenital defects. 

-Airway obstruction and a requirement for multiple operations increase the need for tracheostomy. 

Etiology:

-It is due to mutations in TCOF1, POLR1C, or POLR1D genes. TCOF1 gene mutations are the most common cause of the disorder, accounting for 81 to 93% of all cases. POLR1C and POLR1D gene mutations cause an additional 2% of cases. In individuals without an identified mutation in one of these genes, the genetic cause of the condition is unknown. 

Preoperative Abnormalities:

1. Features may include mandibular and malar hypoplasia, antimongoloid palpebral fissure, macrostomia, irregular maloccluded teeth, microphthalmia, lower lid defects, cleft palate, high arched palate, macroglossia, and auricular deformities. 

2. Associated abnormalities include mental retardation, deafness, dwarfism, cardiac defects, choanal atresia, and skeletal deformities. 

3. Chronic upper respiratory tract obstruction and obstructive sleep apnea, which can lead to growth retardation and/or cor-pulmonale. 

Anesthetic Problems:

1. Upper airway obstruction: in neonates, this may require urgent temporary maneuvers, such as stitching the tongue to the lower lip 

2. Excess secretions: may impede induction of anesthesia 

3. Inhalational induction: may be difficult 

4. Difficult tracheal intubation 

5. Obstructive sleep apnea may occur postoperatively 

6. Pulmonary edema 

Intraoperative Management:

Recommendations:

1-Monitoring by pulse oximetry, to detect airway obstruction, is crucial. 

2-Avoid respiratory depressant drugs, both for premedication and postoperatively 

3-Use drying agents 

4-Never give muscle relaxant until the airway has been secured. 

Airway Management:

-Several methods have been proposed to overcome the problem of difficult intubation, some in the awake patient and some under general anesthesia: 

a) In Awake Patients: 

1-Awake intubation or awake direct laryngoscopy to visualize the vocal cords. 

2-Direct laryngoscopy, with the patient in the sitting position, and using a 5-G feeding tube taped to the side of the laryngoscope to give oxygen. 

3-The Augustine guide (Figure 1): can be used for nasotracheal intubation in an awake, sedated patient.

Figure 1: Augustine guide

4-Fibreoptic bronchoscope or Tracheostomy under local anesthesia: 

In small infants, the ‘tube over bronchoscope’ technique is not always possible because of the small size of the tube, therefore a Seldinger-type approach may be necessary: 

-After the administration of atropine, ketamine IM, and topical lidocaine, a fibreoptic bronchoscope (OD 3.6mm, L 60 cm, and suction channel 1.2 mm) was passed through one nostril. 

-The tongue was held forward with Magill forceps, until the vocal cords were seen, but not entered, because of the risk of total obstruction. 

-Under direct vision, a Teflon-coated guidewire with a flexible tip was passed via the suction channel into the trachea. 

-The bronchoscope was carefully removed leaving the wire in place, and an ID 3mm nasotracheal tube was then passed over it into the trachea. 

Pediatric bronchoscopes of 2.5 mm diameter are now available, but their very fineness makes them less easy to handle than the 4-mm bronchoscopes). 

b) In Anesthetized Patients: 

1-Jackson anterior commissure laryngoscope (Figure 2): 

-The head is elevated above the shoulders, with flexion of the lower cervical vertebrae and extension at the atlanto-occipital joint. The laryngoscope is introduced into the right side of the mouth. Only the tip is directed towards the midline, the proximal end remaining laterally so that a further 30 degrees of anterior angulation can be obtained. 

-The narrow, closed blade prevents the tongue from falling in and obscuring the view of the larynx. When visualized, the epiglottis is elevated, and the larynx is entered. Intubation is then achieved by passing a lubricated tube, without its adaptor, down the laryngoscope. It is held in place with alligator forceps whilst the laryngoscope is withdrawn.

Figure 2: Jackson anterior commissure laryngoscope

2-The Bullard intubating laryngoscope (Figure 3):

-It can be used to achieve nasotracheal intubation.

Figure 3: Bullard intubating laryngoscope

3-Tactile nasal intubation: 

-Inhalational induction with sevoflurane, and the tongue is pulled downwards and forwards. The tube is initially used as a nasal airway, whilst the index and middle finger are used to palpate the epiglottis, through which the tube is then passed. 

4-Laryngeal mask airway: 

-Inserted under propofol anesthesia and can be used as a conduit for the passage of a fibreoptic bronchoscope.

5-The use of an assistant to pull out the tongue with Magill forceps, and at the same time to apply cricoid pressure, to assist laryngoscopy. 

Postoperative Management:

-The tracheal tube should remain in place until the patient is fully awake. 

-Patients should be nursed in a high-dependency area postoperatively. The combination of sleep apnea and drugs with CNS-depressant effects may make them particularly susceptible to respiratory arrest.

Read more ☛ Pierre Robin Syndrome

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Bone Cement Implantation Syndrome (BCIS)

Bone Cement Implantation Syndrome (BCIS)

Bone Cement constituents:

-Bone cement is an acrylic polymer that is formed by mixing two sterile components: 

a) Powder:

1-Polymer: Polymethyl methacrylate/co-polymer (PMMA) 

2-Initiator: Benzoyl peroxide (BPO) 

b) Liquid:

1-Monomer: Methyl methacrylate (MMA) 

2-Accelerator: N, N-Dimethyl para-toluidine (DMPT)/diMethyl para-toluidine (DMpt) 

-To make the cement radiopaque, a contrast agent is added, either zirconium dioxide (ZrO₂) or barium sulphate (BaSO₄). 

-When the two components are mixed, the liquid monomer polymerizes around the pre-polymerized powder particles to form hardened PMMA. During this polymerization process, heat is generated, due to an exothermic reaction, and reaches temperatures of around 82–86 °C. 

Incidence:

-The incidence of BCIS in cemented orthopedic procedures is approximately 20%. 

-The incidence of a severe reaction resulting in cardiovascular collapse within this group is 0.5-1.7%. 

Orthopedic procedures incidence:

-Cemented hemiarthroplasty (highest incidence) 

-Total hip replacement 

-Knee replacement surgery 

BCIS typically occurs during:

-Bone cementation and prosthesis insertion 

-Femoral reaming (before cementation) 

-Joint reduction and limb tourniquet deflation (after cementation) 

Patients at high risk of cardio-respiratory compromise:

-Male sex 

-Increasing age 

-ASA class III / IV 

-Significant cardiopulmonary disease 

-Chronic obstructive pulmonary disease 

-Use of diuretics 

-Use of warfarin 

Conditions that can increase the incidence of BCIS:

-Osteoporosis, Bone metastasis, and Concomitant hip fractures. 

These conditions may be associated with increased or abnormal vascular channels, through which marrow contents can more readily migrate into the circulation, resulting in emboli. 

Pathophysiology of BCIS:

a) Embolization of the Medullary Contents:

-During surgical cementation and prosthesis insertion, the cement is intentionally pressurized to force it into the interstices of the bone, to improve bonding between the cement and bone. 

-The cement then expands in the space between the bone and the prosthesis, further pressurizing air and the medullary contents, forcing them into circulation. These embolic contents include fat, marrow, cement, air, bone particles, and aggregates of platelets and fibrin. 

-When these medullary contents embolize, they may reach the lungs, heart, and/or coronary circulation, causing the characteristic hypoxia and right ventricular dysfunction, leading to hypotension. 

b) Histamine release, Hypersensitivity, and Complement activation:

-Contact with bone cement (Methyl Methacrylate), leads to an increase in blood levels of anaphylactoid complements (C3a and C5a) and histamine, which are potent mediators of vasoconstriction and bronchoconstriction. 

-These mediators result in an increase in pulmonary vascular resistance, causing ventilation/perfusion disturbances, hypoxia, right ventricular failure, and cardiogenic shock. 

Clinical Picture:

-Hypoxia 

-Sudden loss of arterial blood pressure 

-Pulmonary hypertension 

-Arrhythmias 

-Loss of consciousness 

-Cardiac arrest 

-Under general anesthesia, a significant drop in systolic blood pressure (SBP) may herald cardiovascular collapse, whilst a sudden drop in end-tidal pCO₂ may indicate right heart failure leading to a catastrophic reduction in cardiac output. 

-In an awake patient under a regional anesthetic, early signs of BCIS may include dyspnea and/or altered sensorium. 

BCIS Severity Spectrum:

a) Non-fulminant BCIS:

-Characterized by a significant, yet transient, reduction in arterial oxygen saturation and SBP in the peri-cementation period. 

b) Fulminant BCIS:

-With profound intraoperative cardiovascular changes, progressing to; arrhythmias, shock, or cardiac arrest. 

Classification of BCIS Severity: based on the degree of hypoxia, hypotension, and conscious level (Table 1)

Table 1: Classification of BCIS Severity

Prophylaxis:

a) Anesthesia:

1-Ensure adequate hemodynamic optimization pre- and intra-operatively 

2-Keep SBP within 20% of the pre-induction value 

3-Prepare vasopressors in case of cardiovascular collapse 

4-Confirm awareness that cement is about to be prepared/applied 

5-Maintain vigilance for cardiorespiratory compromise 

b) Orthopedic:

1-Inform the anesthetist before cement application 

2-Wash and dry the femoral canal 

3-Apply cement retrograde, utilizing a suction catheter and intramedullary plug in the femoral shaft 

4-Avoid excessive pressurization (3rd generation technique) 

Management:

-Administration of 100% inspired oxygen is first-line therapy, with airway control if necessary. 

-Invasive hemodynamic monitoring (if not already in place), should be established. 

-In cases of severe BCIS (when the patient has been arrested, or in a peri-arrest condition), standard advanced cardiopulmonary life support (ACLS) algorithms and procedures should be followed. 

-Fluid resuscitation to maintain Rt. Ventricle preload, and inotropes to support ventricular contractility.

-Vasopressors (such as Phenylephrine and Noradrenaline) primarily cause peripheral vasoconstriction, and increase aortic blood pressure, which in turn supports coronary artery blood flow, and thus improves myocardial perfusion and contractility. 

-Use of vasopressors and inotropes should be continued into the postoperative period as necessary, under the management of the intensive care unit (ICU).

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CHARGE Syndrome

Anesthetic Management of Pt. with CHARGE Syndrome

Definition:

➧ A syndrome characterized by: 

1-Coloboma of the eye (Figure 1) 

2-Heart defects (ASD, VSD, PDA, TOF, Rt. Aortic arch, Double outlet Rt. ventricle) 

3-Atresia of the choanae (Figure 2) 

4-Retarded growth development and/or central nervous system abnormalities 

Severe sensorineural, visual, and vestibular deficits are suggested as the cause of delay in walking development, rather than retardation. 

5-Genital hypoplasia in males (Hypogonadism) 

6-Ear anomalies (Figure 3) and/or deafness (Figure 4) 

➧ Diagnosis is made on the presence of at least four of the criteria.

Figure 1: Coloboma of iris

Figure 2: Atresia of the choanae

Figure 3: Ear anomalies

Figure 4: Deafness (BAHA)

➧ Other abnormalities include:

Muscular hypotonia, facial palsy, tracheo-oesophageal fistula, cleft lip and palate, micrognathia, laryngomalacia, pharyngolaryngeal hypotonia (inability to maintain the patency of the pharyngolaryngeal passage), subglottic stenosis and other upper airway abnormalities. 

➧ There is a high incidence of abnormal blood gas levels and sleep problems. Cardio-respiratory arrest is common in this group of patients. 

➧ Gastroesophageal reflux has been reported. 

➧ Anesthesia may be required for choanal atresia repair, cardiac surgery, tracheoesophageal fistula, ear surgery, Nissen’s fundoplication, and tracheostomy.

Anesthetic Management:

Preoperative Management: 

1. Preoperative assessment of congenital cardiac defects. 

2. Preoperative assessment of upper airway abnormalities. Pharyngo-laryngeal hypotonia causes variable obstruction, which becomes more pronounced during sleep and during inspiration. 

3. Precautions against aspiration of gastric contents. 

Intraoperative Management: 

1. A range of sizes of endotracheal tubes should be available due to subglottic stenosis. 

2. If micrognathia is present, inhalational induction is advisable. 

3. Tendency for upper airway collapse during light anesthesia due to laryngomalacia or pharyngolaryngeal hypotonia. Edematous arytenoids may result from gastroesophageal reflux. 

4. Tracheal intubation difficulties have been recorded and intubation problems are increased with increasing age. 

5. Tracheostomy may be required for long-term management. Some authors felt that early tracheostomy helped to avoid hypoxemic events in infancy. 

Postoperative Management: 

1. Postoperative monitoring of apnea. 

2. Feeding difficulties and a high incidence of gastroesophageal reflux. 

Postoperative Mortality: 

1. Apnea due to pharyngolaryngeal hypotonia. 

2. Postoperative deaths were frequently associated with pulmonary aspiration. 

3. Patients require multiple anesthetics, with an increased incidence of postoperative mortality.

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Sodium Nitroprusside Toxicity

Sodium Nitroprusside Toxicity:

Mechanism of Action:

After parenteral injection, sodium nitroprusside enters red blood cells, where it receives an electron from the iron (Fe⁺²) of oxyhemoglobin. This non-enzymatic electron transfer results in unstable nitroprusside radical and methemoglobin (Hb Fe⁺³). The former moiety spontaneously decomposes into five cyanide ions and the active nitroso (NO) group. 

The cyanide ions can be involved in one of three possible reactions: 

1) Binding to methemoglobin to form cyan-methemoglobin.

2) Undergoing a reaction in the liver and kidney catalyzed by rhodanase enzyme to form thiocyanate + thiosulfate.

3) Binding to tissue cytochrome oxidase, which interferes with normal oxygen utilization.

N.B. Sodium nitroprusside toxicity is usually related to prolonged administration or occurs in patients with renal or hepatic failure. 

Mechanisms of Toxicity:

1) Direct vasodilation: resulting in hypotension and dysrhythmias (most common).

2) Thiocyanate toxicity: (occurs infrequently).

3) Cyanide toxicity: (in rare cases).

4) Methemoglobinemia: (in very rare cases).

Thiocyanate toxicity :

Symptoms:

Anorexia, nausea, abdominal pain, fatigue, and mental status changes, including psychosis, weakness, seizures, tinnitus, and hyperreflexia. 

Treatment: 

-Toxicity can be minimized by avoiding prolonged administration of nitroprusside and by limiting drug use in patients with renal insufficiency (as thiocyanate is usually excreted in the urine). 

-Thiocyanate can be removed by dialysis (if necessary). 

Cyanide toxicity:

-An early sign of cyanide toxicity is the acute resistance to the hypotensive effects of increasing doses of sodium nitroprusside (tachyphylaxis). (It should be noted that tachyphylaxis implies acute tolerance to the drug following multiple rapid injections, as opposed to tolerance, which is caused by more chronic exposure). 

-Acute cyanide toxicity occurs when the cyanide ions bind to tissue cytochrome oxidase and interfere with normal oxygen utilization. This leads to metabolic acidosis, cardiac arrhythmias, and increased venous oxygen content (as a result of the inability to utilize oxygen). 

Symptoms: 

-Cyanide toxicity is often associated with the odor of almonds on breath and can result in metabolic acidosis, tachycardia, mental status changes, respiratory arrest, coma, and death. 

Treatment: 

-Cyanide toxicity can usually be avoided if the cumulative dose of sodium nitroprusside is less than 0.5 mg/kg/h. 

-Mechanical ventilation with 100% oxygen to maximize oxygen availability. 

-Administering sodium thiosulfate (150 mg/kg over 15 min) or 3% sodium nitrate (5 mg/kg over 5 min), which oxidizes hemoglobin to methemoglobin, or by limiting the administration of nitroprusside. 

Methemoglobinemia:

-Methemoglobinemia occurs due to excessive doses of sodium nitroprusside or sodium nitrate, if the level is greater than 15 %, it can result in symptomatic cellular hypoxia.

Treatment: 

-Methylene blue (1–2 mg/kg of a 1% solution over 5 min), which reduces methemoglobin to hemoglobin.

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Carcinoid Crisis

Carcinoid Crisis

Definition:

-Carcinoid crisis is the most serious and life-threatening complication of carcinoid syndrome and is generally found in people who already have carcinoid syndrome.

-Carcinoid crisis occurs when all of the symptoms of carcinoid syndrome come at the same time. 

Causes:

➧ Spontaneous 

➧ Precipitating factors: 

-Stress, Sympathetic stimulation 

-Hypotension 

-Histamine-releasing drugs 

-Tumour manipulation 

-Regional anesthesia due to hypotension 

-Infection 

-Chemotherapy 

Clinical picture:

-Tachycardia, Arrhythmia 

-Hypotension, Shock 

-Flushing, Hyperthermia 

-Bronchospasm 

-Abdominal pain, Diarrhea 

Management:

Inhibit growth h. & vasoactive peptides release:

-Somatostatin analogs (Octreotide, Lanreotide) 

Anti-serotonin:

-Methesergide, Ketanserin, Cyproheptadine, Ondansetron, Alpha-methyl dopa 

Anti-kallikrein:

-Corticosteroids, Aprotinin

Anti-histamine:

-H1 blockers (Diphenhydramine) & H2 blockers (Ranitidine) 

R of Bronchospasm:

-Salbutamol, Aminophylline 

R of Diarrhea:

-Loperamide 

R of Hypotension:

-Vasopressin, Phenylephrine 

R of Hypertension:

-Alpha-blockers, Beta-blockers 

R of Rt. Heart failure:

-Digitalis, Diuretics

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Drugs Avoided in Patients with Renal Failure

Drugs Avoided in Patients with Renal Failure

➧ The excretion of water-soluble drugs and their active metabolites will be impaired. For drugs that are renally excreted the half-life increases slowly with deteriorating renal function until severe nephron loss at which point the half-life increases sharply with further reductions in renal function. Dialysis can only usually replace a small part of the excretory capacity of the healthy kidney. 

Antibacterial agents:

1-Injectable penicillin G or carbenicillin: may be associated with neuromuscular toxicity, myoclonus, seizures, or coma. 

2-Vancomycin 

3-Amphotericin 

4-Tetracyclines: except doxycycline (Vibramycin), have an antianabolic effect that may significantly worsen the uremic state in patients with severe disease. 

5-Aminoglycosides 

6-Imipenem/cilastatin (Primaxin): can accumulate in patients with chronic kidney disease, causing seizures if doses are not reduced. 

7-Sulphonamides 

8-Nitrofurantoin (Furadantin): has a toxic metabolite that can accumulate in patients with chronic kidney disease, causing peripheral neuritis. 

Anesthetic drugs:

1-Muscle relaxants:

➧ Depolarizing muscle relaxant:

-Suxamethonium: should be avoided if hyperkalemia is present. 

➧ Non-depolarising muscle relaxants (NDMRs): 

-NDMRs depend on the kidney for elimination)

-Gallamine: should be avoided 

-Pancuronium, pipecuronium, alcuronium, curare, and doxacurium: should be used with caution. Potentiation of neuromuscular blockade may occur in the presence of metabolic acidosis, hypokalemia, hypermagnesemia, or hypocalcemia and with medications such as aminoglycosides. Monitor neuromuscular blockade whenever possible. 

-Vecuronium and mivacurium: are safe to use in renal failure as only small percentages are excreted renally.

2-Opioids:

-Morphine: is metabolized in the liver to morphine-6-glucuronide which has about half the sedative effect of morphine with a markedly prolonged half-life. 

-Pethidine: is partially metabolized to norpethidine which is less analgesic and has excitatory and convulsant properties. 

-Tramadol and codeine: Metabolites can accumulate in patients with chronic kidney disease, causing central nervous system and respiratory adverse effects.

3-Inhalational agents:

➧ There is decreased elimination of the fluoride ions which are significant metabolites of enflurane, sevoflurane, and methoxyflurane which can worsen renal function, so these inhalational agents should be avoided especially if used at low flows. 

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs):

➧ NSAIDs should be avoided as all decrease renal blood flow and may precipitate complete renal failure. 

➧ Adverse renal effects of NSAIDs include acute renal failure; nephrotic syndrome with interstitial nephritis; and chronic renal failure.

➧ The risk of acute renal failure is three times higher in NSAID users than in non-NSAID users.

➧ Other adverse effects of NSAIDs include decreased potassium excretion, which can cause hyperkalemia, and decreased sodium excretion, which can cause peripheral edema, elevated blood pressure, and decompensation of heart failure.

➧ NSAIDs can blunt antihypertensive treatment, especially if beta-blockers, ACE inhibitors, or ARBs are used.

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Drugs affecting IOP

Drugs affecting IOP

➧ Normal intraocular pressure (IOP) is between (10 - 20 mmHg). The average value of IOP is 15.5 mmHg with fluctuations of about 2.75 mmHg.

➧ IOP also varies with other factors such as heart rate, respiration, fluid intake, systemic medication, and topical drugs.

➧ Intraocular vascular tone is predominantly affected by CO₂; hypocarbia decreases IOP through vasoconstriction of the choroidal blood vessels and decreases the formation of aqueous humor through reduced carbonic anhydrase activity. The increased IOP associated with hypoventilation and hypercarbia occurs as a result of vasodilation of CBV and increases in central venous pressure. 

A) Drugs that ↑ IOP:

1-Steroid-induced glaucoma:

Mechanism:

Is a form of open-angle glaucoma that is usually associated with topical steroid use, but it may develop with inhaled, oral, intravenous, periocular, or intravitreal steroid administration. 

Risk factors:

-Preexisting primary open-angle glaucoma

-Family history of glaucoma

-High myopia, diabetes mellitus

-History of connective tissue disease (especially rheumatoid arthritis). 

➧ Patients on chronic corticosteroid therapy can remain undiagnosed with an elevated IOP, which can result in glaucomatous optic nerve damage. 

➧ Steroid-induced IOP elevation typically occurs within a few weeks of beginning steroid therapy. In most cases, the IOP lowers spontaneously to the baseline within a few weeks to months upon stopping the steroid. In rare instances, the IOP remains elevated.

2-Topical anticholinergic or sympathomimetic dilating drops, TCA, MAOI, antihistamines, antiparkinsonian drugs, antipsychotic medications, and antispasmolytic agents:

Mechanism:

These medications produce pupillary dilation and precipitate an attack of acute angle-closure glaucoma in anatomically predisposed eyes that have narrow angles. 

3-Sulfa containing medications:

Mechanism:

Induce anterior rotation of the ciliary body causing angle-closure glaucoma. Typically, the angle closure is bilateral and occurs within the first several doses of the sulfonamide-containing medication. Patients with narrow or wide-open angles are potentially susceptible to this rare and idiosyncratic reaction.

4-Ketamine: 

The effect on IOP varies. Early studies reported an increase in IOP after IV or IM administration of ketamine. Ketamine given after premedication with diazepam and meperidine does not affect IOP and IM administered ketamine may even lower IOP in children. 

5-Depolarizing muscle relaxants (Succinylcholine):

Causes a transient (4–6 min) but significant increase in IOP of (10 - 20 mm Hg). Although the mechanism is unclear, the increase is not attributable simply to induced muscle fasciculations. 

6-Large volume Local anesthetic:

Injecting a large volume (8–10 mL) of Local anesthetic into the orbit (e.g. peribulbar block).

7-Tracheal intubation:

Sympathetic cardiovascular responses to tracheal intubation. 

8- Caffeine

B) Drugs that ↓ IOP:

In general, CNS depressants lower IOP.

1-Intravenous anesthetics and volatile agents:

Mechanism:

Relax extraocular muscle tone, depress the CNS (i.e., the diencephalon), improve the outflow of aqueous humor, and lower venous and arterial blood pressures.

➧ e.g. thiopental, propofol, etomidate, decrease in IOP by 14 - 50 % have been noted.

➧ During controlled ventilation and normocapnia, volatile inhaled anesthetics reduce IOP in proportion to the depth of anesthesia.

2-Non depolarizing neuromuscular blocking drugs:

Either do not affect IOP or produce a slight decrease.

3-Benzodiazepines:

IV administered diazepam (0.15 mg/kg) and equipotent intravenous doses of midazolam (0.03 mg/kg).

4-Narcotic premedication:

Causes no change, or only a slight decrease, in IOP. 

5-Neuroleptanalgesia:

Produced by mixtures of (fentanyl and droperidol) decreases IOP by 12 % in normocapnic patients. 

6- Alcohol consumption:

This leads to a transient decrease in IOP.

7- Several pretreatment regimens:

➧ IV lidocaine (1.5 mg/kg) or sufentanil (0.05–0.15 µg/kg) given 3 - 5 min. before induction. 

➧ Oral administration of the centrally acting antihypertensive drug clonidine (5 µg/kg) 2 hrs before induction of anesthesia blunts the IOP response to intubation. 

➧ Intranasal administration of nitroglycerin

➧ β-adrenergic receptor blocking drugs

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