Critical Care

· AC (Assist Control): On AC rate 12 with TV 700, patient will receive 12 ventilator delivered breaths/minute, each with a volume of 700 cc. If the patient initiates a breath on his/her own, the vent will also deliver volume of 700 cc. Tachypnea in this mode may cause respiratory alkalosis.

· SIMV (Synchronized Intermittent Mandatory Ventilation): On SIMV rate 12 with TV 700, patient will receive at least 12 breaths/min, each with volume of 700cc. If patient initiates > 12 breaths/min, the vent provides no support during those breaths unless pressure support is added. This mode prevents over-ventilation in patients with rapid respiratory rates; however, SIMV requires more respiratory muscle work than AC.

· PCV (Pressure Controlled Ventilation): Set the PEEP and initial rate. Then adjust inspiratory pressure to obtain desired tidal volume. Watch for patient agitation (sedate), tachypnea (sedate), and auto-PEEP (reduce set rate or inspiratory time).

· PS (Pressure Support): Patient initiates a breath, which is then supported by vent at preset pressure. Not to be used just post-intubation or in full ventilatory failure because PS provides only partial ventilatory support. PS may be combined with SIMV to provide support during patient initiated breaths.

· CPAP (Continuous Positive Airway Pressure): Vent maintains constant positive pressure during entire respiratory cycle. This is equivalent to setting PEEP to the desired CPAP level and setting pressure support to zero.

3. Initial vent settings:

· Mode: AC or SIMV.

· Rate = 12 (lower rate in COPD/asthma).

· VT = 8-10cc/kg (if in ARDS, see Critical Care: ARDSNet Protocol)

· I:E ratio: no less than 1:2; up to 1:4.

· F_iO₂ = 1.0 (wean down rapidly to < 60% to avoid oxygen toxicity).

· PS (pressure support) = 5-10 (5cm H₂0 needed to overcome resistance of endotracheal tube).

· PEEP (positive end-expiratory pressure) = 0-15 (start low; cautious use in asthmatics and COPD patients as “autoPEEP” occurs often).

4. Adjusting ventilator settings: a simplistic approach

· Low pO₂: increase F_iO₂, increase PEEP (to recruit more alveoli).

· High pCO₂ : increase TV or increase rate (suction, bronchodilators).

5. Weaning parameters

· Initial indication for ventilator (e.g. pneumonia) is resolving.

· The patient is medically stable and alert; sedation weaned to minimal level.

· Adequate pO₂ (> 60) on < 40% F_iO₂.

· Minute ventilation < 10 L/min.

· Respiratory rate < 20.

· Tobin index: respiratory rate (spontaneous) < 105

tidal volume (L)

· Dead space < 50%.

· MIF (maximal inspiratory force) < – 20 (the more negative, the better).

6. Weaning modes (No proven superior method)

Preferred method: spontaneous breathing trial, T-piece or CPAP x 1-2 hours, check Tobin Index.
Decrease SIMV rate (2-4 breaths/min Q12h) ® decrease PS ® T-piece trials.
PS wean by decreasing PS until patient on CPAP (i.e., IPAP=PEEP)
During weaning, follow ABG, RR, HR and BP to determine when extubation is appropriate.

7. Failure to wean:

·	F	Fluid overload® diurese if indicated.
·	A	Airway resistance® check endotracheal tube; is it obstructed or too small?
·	I	Infection® treat as indicated.
·	L	Lying down, bad V/Q mismatch® elevate head of bed.
·	T	Thyroid, toxicity of drugs® check TFT’s, check med list.
·	O	Oxygen ® increase F_iO₂ as patient is taken off ventilator.
·	W	Wheezing ® treat with nebs.
·	E	Electrolytes, eating ® correct K/Mg/PO₄/Ca; provide adequate nutrition.
·	A	Anti-inflammatory needed? ® consider steroids in asthma/COPD.
·	N	Neuromuscular disease, neuro status compromised ® think of myasthenia gravis, ALS, steroid/paralytic neuropathy, etc; assure that patient is in fact awake and alert.

Tobin MJ. Advances in mechanical ventilation. N Engl J Med 2001; 344:1986-96.

NONINVASIVE POSITIVE PRESSURE VENTILATION (NIPPV)

1. The evidence: A recent meta-analysis of 15 RCT’s that studied patients with acute respiratory failure showed that NIPPV reduces mortality, need for mechanical ventilation, and hospital length of stay. There was a relative risk reduction in mortality of 45% (NNT=13) overall and 61% (NNT = 8) in the COPD subgroup.

2. Indications for NIPPV:

· Works best in patients with acute-on-chronic lung disease who have hypercapnic respiratory failure (gives patients bigger tidal volumes and lessens the effort required by the patient).

· First-line treatment for COPD exacerbation (improves hypoxemia, hypercapnia, acidosis, reduces need for intubation, shortens length of stay, and improves survival).

· Acute CHF: decreases afterload, improves oxygenation, improves dyspnea. Watch for ischemia in vulnerable patients. These patients should be monitored closely and should be receiving maximal pharmacologic therapy for their CHF.

· Acute lung injury/ARDS: NIPPV not shown to be effective and can be very harmful in these patients. Only use NIPPV in this situation if patients are at very high risk for infectious complications from intubation/mechanical ventilation. Examples include solid organ transplant recipients and severely immunosuppressed patients.

3. Complications of NIPPV:

· Higher mortality and complications in patients in whom NIPPV is used incorrectly (i.e. patients who meet criteria for intubation/mechanical ventilation at presentation of respiratory failure, acute lung injury, ARDS, etc).

· Nose abrasion, eye irritation, poor patient tolerance.

4. Predictors of failing NIPPV:

· Very low pH on initial ABG.

· Severely altered mental status.

· Higher number of comorbidities.

5. Modes and settings:

· NIPPV is a time-intensive therapy for nurses and respiratory therapists. Make sure that you have adequately trained staff and that they have the time to spend with your patient. In general, these patients should be monitored frequently in the ICU or ER setting.

· Always use full face mask (mouth and nose) when possible to minimize air leaks and nasal resistance at least for the first few hours of NIPPV. If patient improves and is not a “mouth breather”, you can then switch to nasal mask for patient comfort.

· CPAP (Continuous Positive Airway Pressure): generally not indicated for patients with acute respiratory failure. This mode (at a setting of 5-10 cm H₂0) is used mainly for patients with obstructive sleep apnea. There is some data showing benefit with CPAP for CHF exacerbation.

· BiPAP (Bi-level Positive Airway Pressure): provides higher set pressure during inspiration and lower set pressure during expiration (PEEP). When writing for BiPAP, include mode of delivery (face mask or nasal mask), pressure settings (i.e., 10/5 cm H₂0), F_iO₂ , length of trial.

Peter JV, Moran JL, Phillips-Hughes J, Warn D. Noninvasive ventilation in acute respiratory failure—a meta-analysis update. Crit Care Med 2002; 30:555-62.

Brochard L. Noninvasive ventilation for acute respiratory failure. JAMA 2002; 288:932-5.

RAPID SEQUENCE INTUBATION

1. Rapid sequence intubation (RSI) refers to a specific technique using anesthesia, muscle relaxants, and intubation in patients that are high risk for aspiration (emergency intubation). There are 3 major assumptions during RSI: the patient has a full stomach (high risk for aspiration), the operator has the skill to secure the airway, and the operator can resuscitate the patient. Always have back-up close by whenever possible.

2. Does this patient really meet criteria for intubation? Consider intubation only if the patient is apneic, cannot maintain their airway, cannot protect their airway (GCS < 8), cannot be appropriately ventilated, cannot be appropriately oxygenated, or must be intubated for a specific condition or treatment (e.g. going to the O.R.).

3. What is the easiest way to correct the airway problem? Always consider alternatives to intubation.

· Try positioning the patient for optimal airway.

· Consider inserting a nasal or oral airway.

· Consider naloxone if the patient has overdosed on opiates or has been on opiates in the recent past.

· Consider NIPPV (see Critical Care: Noninvasive Positive Pressure Ventilation).

· If intubation is necessary, always consider local anesthesia to the oropharynx and airway without neuromuscular blockade before proceeding with RSI.

4. Equipment and setup required for RSI:

· ICU or ER setting, cardiac monitoring, and pulse oximetry and/or arterial line.

· Bag-valve mask.

· Suction (hook it up and make sure it works).

· Working oxygen supply.

· Laryngoscope with functioning light (test it) and multiple blades of varying sizes.

· Multiple endotracheal tubes of varying sizes along with stylet (always check cuff).

· Working IV access and appropriate medications (sedation, muscle relaxants, atropine, code cart).

· Alternative airway equipment (cricothyroidotomy kit).

5. Pre-oxygenation: gives you a 3-5 minute window of appropriate oxygenation during apnea.

· Replaces the patients functional residual capacity (FRC) with oxygen and washes out nitrogen.

· If possible, always place patient on 100% non-rebreather (NRB) mask if the patient is spontaneously ventilating.

· Use bag-valve mask only if necessary. Avoid prolonged assisted respirations with the bag-valve mask which causes gastric distention and makes aspiration more likely.

6. Medicate: the goal is to reduce the normal physiologic response to laryngoscopy and intubation (high cardiac stress and increased intracranial pressure).

· Sedation first: typically, for medical patients, best agent is etomidate because of safer cardiovascular profile (see Critical Care: Sedatives).

· Muscle relaxant: typically, best agent is succinylcholine because of short duration of effects (see Critical Care: Paralytics).

7. Intubate: always maintain cricoid pressure throughout the procedure to avoid aspiration. Remember to wait for adequate paralysis (~1-2 min). Use multiple modes of checking appropriate airway placement (visualize cords, end-tidal CO₂ monitor, CXR, listen for breath sounds, etc).

SEDATIVES

1. General considerations: always consult your local hospital’s pharmacy guidelines. The doses that are provided are meant only as guidelines—always use your clinical judgement. In addition, only clinicians with adequate experience should be prescribing these agents (call for back-up if necessary).

2. Etomidate: first line sedative for rapid sequence intubation (RSI).

· Dose: 0.3 mg/kg (usual dose ~20 mg IV), onset 20-30 seconds, lasts 5-10 minutes.

· Advantages: rapid onset, short duration, no hypotension, lowers ICP.

· Disadvantages: tendency to induce vomiting (use with paralytic).

· Contraindications: none.

3. Thiopental: great for RSI in neuro patients (high ICP, CVA, status epilepticus).

· Dose: 3-5 mg/kg, onset 30 seconds.

· Advantages: rapid onset, ultra-short acting. Good for neuro patients (does not raise the ICP and is an anti-epileptic).

· Disadvantages: causes hypotension—reduce dose or use alternative sedative.

· Contraindications: severe hypotension.

4. Propofol: fast recovery, so good for patients in whom neuro exam must be checked frequently.

· Dose: RSI dose is 0.5 mg/kg, sedative dose is 1 mg/kg; onset 20 seconds, lasts 8 minutes.

· Advantages: short acting (fast patient recovery); good sedative if patient’s neuro status must be checked frequently (can turn off and check neuro exam in ~10 minutes); some data to suggest use in benzo-refractory delirium tremens.

· Disadvantages: expensive, causes hypotension, depresses myocardial contractility, hypertriglyceridemia. With prolonged use, check triglyceride levels periodically (can lead to pancreatitis).

· Contraindications: use with caution in cardiac patients or hypotensive patients.

5. Midazolam (Versed): great for sedation in the ICU in combination with fentanyl. Also has anti-convulsant properties.

· Dose: 0.5-5.0 mg/hr. Onset 3-5 minutes, can last up to 6 hours. Use lower doses in elderly.

· Advantages: anti-convulsant properties.

· Disadvantages: high risk of respiratory depression. Use with caution if patient not intubated. Moderate hypotension.

· Contraindications: narrow-angle glaucoma.

6. Fentanyl: great for pain control in the intubated patient.

· Dose: bolus 50-200 mcg IV; then start infusion at 25-200 mcg/hr.

· Advantages: pain control. Rapid onset, more potent, less BP effects, and shorter duration than morphine.

· Disadvantages: respiratory depression; prolonged sedation possible if used for > 5 days as the drug accumulates in adipose tissue.

· Contraindications: increased ICP, end-stage liver disease, severe respiratory depression (not yet intubated).

Jacobi J, Fraser GL, Coursin DB, et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med 2002; 30:119-41.

PARALYTICS

· Possible side effects: histamine release (succinylcholine), hypotension, tachycardia, bronchospasm, malignant hyperthermia (treat with dantrolene), prolonged paralysis.

2. Succinylcholine: first line paralytic for RSI. Don’t use in neuro patients or those with hyperkalemia.

· Dose: 1.5 mg/kg (usual dose ~100 mg IV), onset 30-60 seconds, lasts 8-12 minutes.

· Advantages: rapid onset, short-acting.

· Disadvantages: bradycardia (consider atropine), increases ICP, increased chance of vomiting.

· Contraindications: hyperkalemia, ESRD, CVA, spinal cord injury, history of malignant hyperthermia, eye injury, high ICP, rhabdomyolysis.

3. Rocuronium: use when succinylcholine is contraindicated.

· Dose: 0.6-1.2 mg/kg, onset 15-20 seconds, duration 25-60 minutes.

· Advantages: rapid onset, minimal cardiovascular effects, can use if succinylcholine contraindicated. Okay to use in renal and/or liver failure.

· Disadvantages: longer acting.

· Contraindications: none except if patient is allergic to this drug or component of drug.

4. Vecuronium: use when succinylcholine is contraindicated. Don’t use in patients with liver disease.

· Dose: 0.1 mg/kg, onset 2½-3 minutes, lasts 25-40 minutes.

· Advantages: minimal cardiovascular effects, can use if succinylcholine contraindicated.

· Disadvantages: longer acting, can’t use in patients with liver disease.

· Contraindications: cirrhosis, liver dysfunction (can double recovery time). Use with caution in patients with kidney disease (prolonged clearance, although recovery time usually normal).

5. Cisatracurium: use in patients with liver or renal disease.

· Dose: 0.15-0.20 mg/kg, onset 1½-2 minutes, lasts 60 minutes.

· Advantages: drug of choice in patients with hepatic or renal failure, rapid acting.

· Disadvantages: expensive; may not be readily available at all hospitals.

· Contraindications: none except if patient is allergic to this drug or component of drug.

Murray MJ, Cowen J, DeBlock H, et al. Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient. Crit Care Med 2002; 30:142-56.

ARDSNET PROTOCOL

1. Does your patient meet ARDS criteria? Bilateral infiltrates on CXR consistent with pulmonary edema, no evidence of left atrial hypertension—if measured, PCWP < 18 mmHg, and PaO₂/F_iO₂ ratio < 300. ARDS must be acute in onset and patient must require mechanical ventilation.

2. The ARDSNet protocol ventilator settings are very uncomfortable for the patient. Therefore, be ready to give heavy sedation and possibly paralytics to avoid having the patient fight the ventilator.

3. Initial ventilator settings:

Calculate ideal body weight (IBW): for females, IBW = 45.5 + 2.3 (height in inches – 60); for males, IBW = 50 + 2.3 (height in inches – 60).
Set mode to assist-control ventilation (ACV) and set initial tidal volume to 8 cc/kg (IBW). Reduce to 7 cc/kg (IBW) after 1-2 hours and then to 6 cc/kg (IBW) after 1-2 hours.

4. The plateau pressure (P_PL) goal is < 30 cm H₂0. Adjust the tidal volume to reach this goal:

Ask RT to check P_PL with a 0.5 second inspiratory pause q4h and after each change in tidal volume or PEEP.
If P_PL > 30, decrease tidal volume to 5 cc/kg IBW or even 4 cc/kg IBW if necessary.
If P_PL< 25 and the tidal volume < 6 cc/kg IBW, increase tidal volume until P_PL> 25 or tidal volume = 6 cc/kg.
If the patient is breath stacking or has severe dyspnea, tidal volume may be increased to 7 or 8 cc/kg IBW as long as the P_PL< 30.

5. Oxygenation goal = PaO₂ 55-80 mmHg or O₂ sat 88-95% in order to avoid oxygen-induced lung injury. Basically, you’ll want to use a high level of PEEP for any given F_iO₂ setting:

F_iO₂	0.3	0.4	0.4	0.5	0.5	0.6	0.7	0.7	0.7	0.8	0.9	0.9	0.9	1.0
PEEP	5	5	8	8	10	10	10	12	14	14	14	16	18	20-24

6. pH goal = 7.30 – 7.45:

If pH 7.15 – 7.30, increase the set rate until pH > 7.30 or PaCO₂ < 25 (max rate = 35). If the set rate = 35 and the pH is still < 7.30, consider giving NaHCO₃.
If pH < 7.15, set rate to 35. If the set rate = 35 and pH is still < 7.15, consider NaHCO₃. In addition, increase tidal volume at 1 cc/kg IBW increments until pH > 7.15. It is okay to go above the target P_PL at this point.
If pH > 7.45, decrease set rate until patient’s respiratory rate < set vent rate. Minimum set rate=6.

7. The goal I:E ratio is 1:1 – 1:3. Adjust flow rate and inspiratory flow wave-form to achieve this goal.

8. Conduct a weaning trial daily if the patient meets all of the following criteria:

F_iO₂ < 0.4 and PEEP < 8 (as long as these values are < values from previous day).
Patient can take spontaneous breaths (turn down the set vent rate and see).
Systolic BP > 90 mmHg without pressors.

9. For more specifics on the weaning protocol or other inquiries into the ARDSNet studies or protocols, go to http://www.ardsnet.org or http://hedwig.mgh.harvard.edu/ardsnet/.

Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000; 342:1301-8.

TROUBLESHOOTING THE VENTILATOR

1. If the patient is in acute distress, do the following:

· Disconnect the patient from the ventilator.

· Bag ventilate the patient by hand at 100% F_iO_2.

· If the patient is unstable, remember your ABC's.

· Brief physical exam (listen to the lungs).

· Check to see if the airway is patent.

· Rule out pneumothorax, airway obstruction, or lost (unsecured) airway.

· Check peak pressure and plateau pressure (ask RT to show you how):

- High peak pressure and high plateau pressure (stiff lung): consider pulmonary edema, worsening consolidation, ARDS, atelectasis, mainstem intubation, tension PTX, decreased chest wall compliance.

- High peak pressure but low to normal plateau pressure (airway problem): consider bronchospasm, mucous plug, secretions, obstructed tubing, patient biting tube.

- Low peak pressure and low plateau pressure (disconnect problem): consider disconnected tubing, lost airway.

· Order a chest x-ray.

2. Causes of pressure-limited ventilator problems:

Tension pneumothorax ® insert 14 gauge angiocath into 2^nd intercostal space, midclavicular line.
Airway obstruction due to mucous plug, secretions, blood, etc. ® aggressive suction.
Tubing occlusion ® check the tubing in the ventilator circuit.
Mainstem intubation (usually right mainstem) ® pull back the endotracheal tube, check CXR.
Agitation, pain, anxiety, delirium ® treat as indicated.
Massive atelectasis ® recruit more alveoli (increase tidal volume and/or PEEP).
Bronchospasm ® give nebulizers.
Decreased chest wall compliance.
Patient biting tubing or fighting ventilator (i.e. anxious, coughing) ® sedate as needed.

3. Causes of non-pressure limited ventilator problems:

Pneumothorax (non-tension) ® verify with CXR, insert chest tube for decompression.
Disrupted tubing or ventilator malfunction ® fix the problem or get a new ventilator.
Cuff deflation ® re-inflate cuff and confirm positioning.
Lost airway ® re-intubate.
Auto-PEEP ® decrease set rate, decrease set amount of PEEP, decrease I:E ratio (increase flow rate), check for expiratory circuit obstruction.
Pulmonary embolism.
Hemodynamic crisis.

4. Other common ventilator problems:

· Low exhaled volume ® check for cuff leak, bronchopleural fistula, low flow rate.

· Increased respiratory rate ® check for change in the patient's clinical status; draw ABG to assess for need to increase set rate or set tidal volume.

· High minute ventilation ® check for hyperventilation (neurogenic, agitation, incorrect vent settings), hypermetabolic state (sepsis, fever, seizures, acidosis), or inefficient ventilation (increased dead space).

CRYSTALLOIDS VS. COLLOIDS

1. Definitions:

· Crystalloids: IV fluids composed of water and electrolytes (e.g. normal saline (NS), lactated Ringer’s (LR), D₅½NS).

· Colloids: IV fluids composed mainly of larger particles that are relatively impermeable to membranes (e.g. albumin, red blood cell substitutes).

2. Albumin: in critically ill ICU patients, there is no evidence to support the use of albumin. Albumin is more expensive and may be associated with a higher mortality when compared to crystalloids.

· A recently published meta-analysis concluded that in critically ill patients with hypovolemia, burns, or hypoalbuminemia, albumin increases mortality.

· There is data that shows a survival benefit from albumin in cirrhotic patients with spontaneous bacterial peritornitis (SBP).

· Albumin may be useful in preventing progression of renal failure in certain patients (i.e. cirrhosis). However, its use in this setting has not been validated and many believe that albumin use should be restricted to multi-center randomized controlled trials.

3. RBC substitutes: none have been shown to be effective thus far; some may be associated with increased mortality.

4. Hypertonic saline: has been shown to increase myocardial contractility and increase venous return. Used most often in trauma patients. No good data showing a survival benefit.

5. The bottom line: there is no good data to justify the use of colloids except in certain very specific circumstances (albumin for SBP).

Alderson P, Bunn F, Lefebvre C, et al. Human albumin solution for resuscitation and volume expansion in critically ill

patients. Cochrane Database Syst Rev. 2002;(1):CD001208.

Waikar SS, Chertow GM. Crystalloids versus colloids for resuscitation in shock. Curr Opin Nephrol Hypertens. 2000 Sep;9(5):501-4.

ACTIVATED PROTEIN C FOR SEPSIS

Follow link to Infectious Diseases: Activated Protein C for Sepsis.

INITIAL CHOICE OF PRESSOR IN HYPOTENSION

1. General considerations:

First and foremost: fluids, fluids, fluids—especially in septic shock. Of course, use fluids with caution in patients in cardiogenic shock. However, most pressors will have deleterious effects (organ hypoperfusion) if used before adequate fluid resuscitation.
The data for initial choice of pressor in hypotension is scant. Much of the evidence comes from experimental animal models that may not apply to humans.
Although many clinicians choose dopamine as their “first-line” agent, its use has recently been challenged by those who favor phenylephrine and/or norepinephrine.
Do not use “low-dose” or “renal-dose” dopamine. There is ample evidence that shows no benefit in protecting the kidneys or providing a mortality benefit.

2. Simplified Approach: this is just a simple guide; always use your clinical judgment!

	Low Cardiac Output	Normal to High Cardiac Output
Low SVR	Norepinephrine	Phenylephrine
High SVR	Dobutamine	Dopamine

3. Starting doses of specific agents: always consult your local hospital’s pharmacy guidelines. See also Cardiology: Pressors and cardiac drips.

Phenylephrine: 10-200 mcg/min. Consider as first line in low SVR states (septic shock). Always ensure adequate fluid resuscitation and watch for organ hypoperfusion at higher doses.
Norepinephrine: 1-30 mcg/min. Use once patient is adequately fluid resuscitated. One study showed a mortality benefit if this agent was used in patients who were still hypotensive after dopamine was at 15 mcg/kg/min. This agent is probably better than high dose dopamine. It doesn’t cause as much cardiac irritability (arrhythmia) and unlike phenylephrine, does not cause depression of myocardial function. Note: can increase myocardial perfusion by vasodilating coronary arteries.
Dobutamine: 1-20 mcg/kg/min. Used in cardiogenic shock. No mortality benefit.
Dopamine: 1-20 mcg/kg/min. Thought by many to be the “first line” initial pressor for hypotension.
Epinephrine: 0.25-20 mcg/min. Usually used in cardiac arrest. Avoid high dose epinephrine during or after cardiac arrest (no survival benefit). If using in shock, doses above 4 mcg/min give predominantly alpha (vasoconstriction) effect.
Low-dose vasopressin: 0.01-0.05 units/min. Shown in limited studies to be beneficial in patients with vasodilatory septic shock. These patients are vasopressin-deficient and are usually exquisitely sensitive to the effects of low doses of this agent. Consider using it in any patient with refractory distributive (low SVR) shock. Caution: can cause coronary vasoconstriction.

Martin C, Viviand X, Leone M, Thirion X. Effect of norepinephrine on the outcome of septic shock. Crit Care Med 2000; 28:2758-65.

Bellomo R, Chapman M, Finfer S, Hickling K, Myburgh J. Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial. Lancet. 2000 Dec 23-30;356(9248):2139-43.

Holmes CL, Patel BM, Russell JA, Walley KR. Physiology of vasopressin relevant to management of septic shock.

Chest. 2001 Sep;120(3):989-1002.

EARLY GOAL-DIRECTED THERAPY FOR SEPSIS

1. General considerations:

A recent trial showed that in patients with sepsis or septic shock, early goal-directed therapy (rapidly and systematically resuscitating patients) resulted in a 42% relative risk reduction in in-hospital mortality (NNT=6) and a 33% relative risk reduction in mortality at 60 days (NNT=6).
This trial underscored the importance of quick and adequate fluid resuscitation—the patients in the control group died more often from cardiovascular collapse.
Use this protocol only in patients in whom there is a high suspicion of sepsis (obvious source of infection, immunocompromised patients, positive blood cultures, etc).
Remember to always start antibiotics (broad spectrum in most cases) immediately upon consideration of the diagnosis of sepsis.

2. Inclusion criteria:

Must meet at least 2 of 4 criteria for systemic inflammatory response syndrome (SIRS):

- Temperature > 38°C or < 36°C.

- Heart rate > 90 beats per minute.

- Respiratory rate > 20 breaths per minute or PaCO₂ < 32 mmHg.

- WBC > 12,000 cells/mm³ or > 10% bands (immature neutrophils).

Must have either:

- Lactate > 4 mmol/L or

- Systolic BP < 90 mmHg after 20-30 cc/kg fluid resuscitation

3. Exclusion criteria:

Presence of an acute disorder such as seizure, stroke, status asthmaticus, or burn.

4. Protocol:

Initiate protocol as early as possible after diagnosis of sepsis is made and inclusion criteria have been met. In the study, patients were treated with the protocol for the first 6 hours after diagnosis.
Give supplemental oxygen and/or mechanical ventilation as necessary.
Place CVP line (IJ or subclavian site, and catheter capable of continuous central venous oxygen saturation (ScvO₂) monitoring preferable). If no ScvO₂ monitoring capability, can send blood periodically from tip of CVP line for “mixed-venous” O₂ gas.
If intubated, use sedation and paralysis as clinically indicated.
Give crystalloid until CVP 8-12 mmHg.
Check mean arterial pressure (MAP). Goal MAP between 65-90 mmHg. If MAP < 65 mmHg, give pressors.
Check ScvO₂ or send mixed-venous gas from CVP line tip and check oxygen saturation. If ScvO₂ < 70%, transfuse RBC until hematocrit > 30%. If hematocrit > 30% and ScvO₂ still < 70%, start inotropic agent and titrate up until ScvO₂ > 70%.
Once all goals are achieved, give the patient standard ICU care for septic shock.

Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368-77.

HYPOTHERMIA TREATMENT PROTOCOL FOR CARDIAC ARREST

1. Inclusion criteria:

Age 18 years or older
Women must be over 50 or have a negative pregnancy test
Cardiac arrest with return of normal rhythm (initial rhythm: VF or pulseless VT; PEA can be considered if returned to normal rhythm and other criteria met)
Persistent coma as evidenced by no eye opening to pain after resuscitation (no waiting period required)
Blood pressure can be maintained at least 90 mm Hg systolic either spontaneously or with fluid and pressors (not aortic balloon pump)
Known time of cardiac arrest (excludes “found down” of unknown duration)

2. Exclusion criteria:

Another reason to be comatose (e.g. drug overdose, status epilepticus)
Pregnancy
A known terminal illness preceding the arrest
Known, pre-existing coagulopathy or bleeding
No limit on duration of resuscitation effort; however “down time” of less than 1 hour most desirable
Pre-existing DO NOT INTUBATE code status and patient not intubated as part of resuscitation efforts

3. Protocol (goal temperature 33°C as to be achieved as soon as possible):

Patients should be started on protocol as quickly as possible.
Immediately place ice packs under the armpits, next to the neck, on the torso and the limbs.
Temperature sensing Foley catheter should be placed if available, otherwise rectal or tympanic temperatures should be used (in that order).
Two cooling blankets should be used, one under and one over the patient.
The ventilator humidifier should be turned off and a Heat Moisture Exchanger (HME) should be used.
The room thermostat should be turned off.
Administer midazolam 2-6 mg/hour and fentanyl 25-75 mcg/hour
Once sedation is started, give vecuronium 0.1 mg/kg bolus, then start a drip of 1 mg/hour. Titrate the drip 0-5 mg/hr to keep 1/4 twitches.
Patients should be on insulin drip (if glucose > 180 mg/dl), daily aspirin, pressors and/or nitrates to maintain blood pressure, and any anti-arrhythmic necessary.
Patients may receive other cardiac interventions including systemic thrombolysis, anticoagulation, and urgent percutaneous coronary interventions as needed. Hypothermia should proceed concurrent with these interventions.
Once the patient reaches 33°C (bladder, rectal, or tympanic), keep patient at 33°C by removing ice packs and top cooling blanket if necessary.
Begin passive re-warming 24 hours after the beginning of cooling (not 24 hours after target temperature is reached): turn room thermostat up to normal, turn on heater on ventilator, turn off cooling blanket, may use regular blankets.
Do not use warm air blanket unless temp not 36°C after twelve hours of passive rewarming.

· Paralysis, then sedation, may be discontinued during or after rewarming, based on shivering and other critical care issues.

Based on the San Francisco General Hospital Hypothermia after Cardiac Arrest Protocol: 2002.

Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002;346:549-56.

FEVER + CENTRAL LINE

1. Approach:

The following flowchart is one way to approach a fever in the patient with a central line. Remember to always use your clinical judgment for the individual patient.
Note: the algorithm shown below assumes that there are no obvious alternative explanations for the patient’s fever (e.g. new nosocomial pneumonia).

2. Treatment:

· Complicated line infection (endocarditis, osteomyelitis, septic thrombosis): remove central line and give antibiotics for 4-6 weeks (6-8 weeks for osteomyelitis).

· Uncomplicated line infection:

Pathogen	Central line	Antibiotic duration	Notes
S. aureus	Remove	14 days	Strongly consider TEE; if TEE positive, treat with antibiotics for 4-6 weeks
Gram neg rods	Remove	10-14 days
Candida spp.	Remove	14 days after last positive blood culture
Coagulase-negative staph (S. epi)	If line removed	5-7 days
Coagulase-negative staph (S. epi)	If line stays in	10-14 days	Consider treatment with antibiotic lock

Mermel LA, Farr BM, Sherertz RJ, et al. Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis 2001; 32:1249-72.

MECHANICAL VENTILATION

5. Weaning parameters

High SVR