This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
1. Medicine in Mind Maps Medical Science made incredibly
simple
2. abdominal trauma - assessment [created by Paul Young
28/10/07] initial assessment imaging and laboratory studies
definitiontrauma series: - CXR identifies haemothorax, pneumothorax
and pulmonary contusion - AP pelvis can confirm presence of
significant pelvic fracture - lateral c-spine can identify
non-survivable neck injury resuscitation & comprehensive
assessment Primary survey: (i) Airway(ability of air to pass
unobstructed to the lungs): critical findings include: -
obstruction of the airway due to direct injury, oedema, foreign
body or inability to protect the airway because of depressed level
of consciousnesss key treatment is: - establishment of airway (ii)
Breathing (ability to ventilate and oxygenate): key clinical
findings are: - absence of spontaneous ventilation, absent or
asymmetrical breath sounds, dyspnoea hyperresonance, dullness,
gross chest wall instability or defects that compromise ventilation
key conditions to identify are: - pneumothorax, endotracheal tube
malposition, tension pneumothorax, haemothorax, sucking chest
wounds, flail chest key treatment is: - chest tube (iii)
Circulation: key clinical findings are: - collapsed or distended
neck veins, signs or tamponade, external sites of haemorrhage key
conditions identified are: - hypovolaemia, cardiac tamponade,
external haemorrhage key treatment is: - iv access, fluid
resuscitation, compression of sites of bleeding (iv) Disability:
key clinical conditions are: - decreased level of consciousness,
pupillary assymetry, gross weakness key conditions identified are:
- serious head and spinal cord injury key treatment is: -
definitive airway if indicated, emergency treatment of raised icp
(v) Exposure and control of immediate environment: - expose patient
and prevent hypothermia Resuscitation phase: - continues throughout
primary and secondary survey and until treatments are complete -
fluids are required to sustain intravascular volume, tissue and
organ perfusion and urine output - administer blood for
hypovolaemia that is unresponsive to crystalloid boluses - end
points are normal vital signs, absence of blood loss, adequate
urine output and no evidence of end organ dysfunction; blood
lactate and base deficit on an ABG may be helpful in patients who
are severely injured Other procedures: several monitoring and
diagnostic adjuncts occur in concert with the primary survey: (i)
ECG and ventilatory monitoring and continous pulse oximetry (ii)
decompress stomach with NG or OG tube once airway is secured (iii)
insert a foley cather during resuscitation phase (foley catheter
placement is contraindicated if urethral injury is evident as
identified by blood at the meatus, ecchymosis or scrotum or labium
majora or high riding prostate - retrograde urethrogram is required
for these patients) Secondary survey of abdominal trauma: (i)
inspection: - examine for the presence of external signs of injury
noting patterns of abrasion and/or ecchymotic areas - lap belt
bruising is positively correlated with rupture of the small
intestine and increased incidence of other intraabdominal injury
(20-30% of patients with lap-belt marks have associated mesenteric
or intestinal injuries) - bradycardia may indicate free
intraperitoneal blood - Cullen sign (periumbillical ecchymosis) may
indicate retroperitoneal haemorrhage; however, this usually takes
hours to develop - flank bruising and swelling may raise suspicion
for retroperitoneal injury - inspect genitals and peritoneum (ii)
palpation: - fullness may indicate haemorrhage - crepitation of
lower rib cage may indicate hepatic or splenic injury - rectal and
vaginal examination identify potential bleeding and injury - signs
of peritonitis soon after injury suggest leakage of intestinal
contents; peritonitis due to intra-abdominal haemorrhage may take
several hours to develop FAST: - used to identify free fluid in the
peritoneal cavity - FAST has a sensitivity of 70-95% - involves
directing to ultrasound probe in four regions: (i) the subxipoid
location to determine whether there is fluid in the pericardial
space & to make a rough assessment of contractility &
filling state (ii) the right upper quadrant (iii) the splenorenal
recess (iv) the pelvis - problems with FAST: (i) operator dependent
(ii) false negative rate in children is high (iii) technically more
difficult with obesity & sc empysema CT abdo/pelvis: - is the
diagnostic modality of choice for haemodynamically stable patients
- the major reason not to obtain a CT scan is haemodynamic
instability - allows haemoperitoneum & its source to be
identified & allows specific injuries to be graded - CT also
permits evaluation of retroperitoneal structures including the
kidneys, major blood vessels & bony pelvis - the majority of
blunt solid organ injuries are now managed non-operatively in
trauma centres; however, a blush of intravenous contrast agent
indicates active extravasation from a bleeding vessel and is strong
predictor of failure of non-operative management - problems with CT
scanning are: (i) the need to transfer the patient to radiology
(ii) the time associated with transfer and scanning (iii) risks
associated with intravenous contrast agents (iv) the fact hollow
viscus, diaphragmatic & pancreatic injuries are frequently
missed on initial scanning abdominal trauma consists of blunt and
penetrating trauma Penetrating abdominal trauma: - most commonly
injured organs with stab wounds are small intestine, liver and
colon - only one third of abdominal stab wounds penetrate the
peritoneum & only 50% of these require surgical intervention -
85% of abdominal wall gun shot wounds penetrate the peritoneum
& 95% of these require a surgical procedure for correction
Blunt abdominal trauma - spleen and liver are the most commonly
injured organs; small and large intestines are the next most
commonly injured DPL: - has an accuracy of 98% for detection of
haemoperitoneum but does not determine source - generally performed
in patients too unstable for CT - involves performing a
minilaparotomy with placement of a lavage catheter into the
periotoneal cavity directed towards the pelvis - the return of
gross blood is a positive result - if DPL is grossly negative then
1L of warmed saline is instilled into the the abdominal cavity
& then drained back into the intravenous fluid bag by gravity.
The effluent lavage is sent to the laboratory for analysis. -
laboratory criteria for a positive DPL in blunt trauma are: (i)
>100000 RBCs/mm3 (ii) >500 WBC/mm3 (iii) presence of food
particles (iv) presence of bile (v) presence of bacteria - problems
with DPL: (i) an invasive procedure (ii) 1/4 of patients with a
positive DPL will have a non-therapeutic laparotomy (iii) 5% false
negative rate with retroperitoneal, hollow viscus or diaphragm
injuries - ongoing haemorrhage is the most likely cause of
persistent or recurrent haemodynamic instability - initial goal is
not to diagnose specific abdominal organ injury but rather to
determine wheter there are signs & symptoms that indicate a
need for immediate laparotomy 30% of patients with lumbar Chance
fracture have associated bowel or mesenteric injuries criteria for
positive DPL
3. abdo USS cholecystitis obstructed renal tract duplex scan
kidneys FAST post liver transplant duplex USS
5. abnormal ventilator waveforms auto-PEEP alveolar
overdistension cardiac oscillations circuit leaks Normally,
expiratory flow returns to the baseline prior to the next breath.
In the event that the expiratory flow does not return to the zero
line and the subsequent inspiration begins below the baseline,
auto-PEEP or air trapping is present. The presence of auto-PEEP or
air trapping may result from: a. Inadequate expiratory time b. Too
high a respiratory rate c. Long Inspiratory Time d. Prolonged
exhalation due to bronchoconstriction. - The classic sign, known as
"Beak Effect" or "Duckbill" shows an increase in airway pressure
without any appreciable increase in volume. baseline of the
pressure-time waveform shows slight up and down movements with
heartbeat; these may initiate triggering of synchronised breaths
increased airway resistance & decreased lung compliance Normal
curve: - demonstrates normal PIP , Pplat , PTA (transairway
pressure), and Ti (inspiratory time). High Raw: - A significant
increase in the PTA is associated with increased in airway
resistance. High Flow: - the inspiratory time is shorter than
normal, indicating a higher inspiratory gas flow rate. Decreased
Lung Compliance: - An increase in the plateau pressure and a
corresponding increase in the PIP is consistent with decreased lung
compliance. inadequate inspiratory flow - inadequate inspiratory
flow rate on the pressure time waveform leads to a 'scooped out'
appearance to the synchronised breaths there is less volume expired
than inspired baseline of the pressure time waveform drifts
downwards
6. acidosis in kidney disease [created by Paul 15/12/07] Distal
(Type 1) Renal Tubular Acidosis General - This is also referred to
as classic RTA or distal RTA. - The problem here is an inability to
maximally acidify the urine. Typically urine pH remains > 5.5
despite severe acidaemia ([HCO3] < 15 mmol/l). - Some patients
with less severe acidosis require acid loading tests (eg with
NH4Cl) to assist in the diagnosis. If the acid load drops the
plasma [HCO3] but the urine pH remains > 5.5, this establishes
the diagnosis. General Classification of Causes of type 1 RTA
(i)Hereditary (genetic) (ii) Autoimminue diseases (eg Sjogren's
syndrome, SLE, thyroiditis) (iii) Disorders which cause
nephrocalcinosis (eg primary hyperparathyroidism, vitamin D
intoxication) (iv) Drugs or toxins (eg amphotericin B, toluene
inhalation) (v) Miscellaneous - other renal disorders (eg
obstructive uropathy) Pathophysiological Mechanisms in Reduced H+
Secretion in Distal Tubule (i) "Weak pump" - Inability for H+ pump
to pump against a high H+ gradient (ii) "Leaky membrane" -
Back-diffusion of H+ [eg This occurs in RTA due amphotericin B]
(iii) "Low pump capacity" - Insufficient distal H+ pumping capacity
due to tubular damage. Investigation - Typical findings are an
inappropriately high urine pH (usually > 5.5), low acid
secretion and urinary bicarbonate excretion despite severe
acidosis. Renal sodium wasting is common and results in depletion
of ECF volume and secondary hyperaldosteronism with increased loss
of K+ in the urine. - The diagnosis of type 1 RTA is suggested by
finding a hyperchloraemic acidosis in association with an alkaline
urine particularly if there is evidence of renal stone formation.
Note: If [HCO3 > 15 mmol/l, then acid loading tests are required
to establish the diagnosis. Treatment - Treatment with NaHCO3
corrects the Na+ deficit, restores the extracellular fluid volume
and results in correction of the hypokalaemia. Typical alkali
requirements are in the range of 1 to 4 mmol/kg/day. K+ supplements
are only rarely required. Sodium and potassium citrate solutions
can be useful particularly if hypokalaemia is present. Citrate will
bind Ca++ in the urine and this assists in preventing renal stones.
Proximal (Type 2) Renal Tubular Acidosis General - Type 2 RTA is
also called proximal RTA because the main problem is greatly
impaired reabsorption of bicarbonate in the proximal tubule. - At
normal plasma [HCO3], more than 15% of the filtered HCO3 load is
excreted in the urine. When acidosis is severe and HCO3 levels are
low (eg 10 mOsm/l is often stated to be abnormal. Importance of the
type of osmometer - Only osmometers using freezing point depression
method should be used for determining this calculation because they
are the only type of osmometer that can detect all the volatile
alcohols which can abnormally increase the osmolar gap. Vapour
pressure osmometers can't do this Significance of an elevated
osmolar gap - An elevated osmolar gap provides indirect evidence
for the presence of an abnormal solute which is present in
significant amounts. To have much effect on the osmolar gap, the
substance needs to have a low molecular weight and be uncharged so
it can be present in a form and in a concentration (measured in
mmol/l) sufficient to elevate the osmolar gap. - Ethanol, methanol
& ethylene glycol are three such solutes that, when present in
appreciable amounts, will cause an elevated osmolar gap. If you
suspect that your patient may have ingested one of these substances
than you should determine the osmolar gap. - if the ethanol levels
are measured they can be added to the calculated osmolarity to
exclude the presence of an additional contributer to the osmolar
gap. [NB: To convert ethanol levels in mg/dl to mmol/l divide by
4.6. For example, an ethanol level of 0.05% is 50mg/dl. Divide by
4.6 gives 10.9mmols/l] delta ratio Definition - The Delta Ratio is
sometimes useful in the assessment of metabolic acidosis. - The
Delta Ratio is defined as: Delta ratio = (Increase in Anion Gap /
Decrease in bicarbonate) Use - In order to understand this,
consider the following: - If one molecule of metabolic acid (HA) is
added to the ECF and dissociates, the one H+ released will react
with one molecule of HCO3- to produce CO2 and H2O. This is the
process of buffering. The net effect will be an increase in
unmeasured anions by the one acid anion A- (ie anion gap increases
by one) and a decrease in the bicarbonate by one. - if all the acid
dissociated in the ECF and all the buffering was by bicarbonate,
then the increase in the AG should be equal to the decrease in
bicarbonate so the ratio between these two changes (which we call
the delta ratio) should be equal to one. The delta ratio quantifies
the relationship between the changes in these two quantities. - the
above assumptions about all buffering occurring in the ECF and
being totally by bicarbonate are not correct. Fifty to sixty
percent of the buffering for a metabolic acidosis occurs
intracellularly. This amount of H+ from the metabolic acid (HA)
does not react with extracellular HCO3- so the extracellular
[HCO3-] will not fall as far as originally predicted. The acid
anion (ie A-) however is charged and tends to stay extracellularly
so the increase in the anion gap in the plasma will tend to be as
much as predicted. - Overall, this significant intracellular
buffering with extracellular retention of the unmeasured acid anion
will cause the value of the delta ratio to be greater than one in a
high AG metabolic acidosis. Sources of error: - Inaccuracies can
occur for several reasons, for example: (i) Calculation requires
measurement of 4 electrolytes, each with a measurement error (ii)
Changes are assessed against 'standard' normal values for both
anion gap and bicarbonate concentration. Assessment < 0.4 -
Hyperchloraemic normal anion gap acidosis - A low ratio occurs with
hyperchloraemic normal anion gap acidosis. The reason here is that
the acid involved is effectively hydrochloric acid (HCl) and the
rise in plasma [chloride] is accounted for in the calculation of
anion gap (ie chloride is a 'measured anion'). - The result is that
the 'rise in anion gap' (the numerator in the delta ration
calculation) does not occur but the 'decrease in bicarbonate' (the
denominator) does rise in numerical value. - The net of of both
these changes then is to cause a marked drop in delta ratio,
commonly to < 0.4 0.4 - 0.8 - Consider combined high AG &
normal AG acidosis BUT note that the ratio is often 2 - A high
delta ratio can occur in the situation where the patient had quite
an elevated bicarbonate value at the onset of the metabolic
acidosis. Such an elevated level could be due to a pre-existing
metabolic alkalosis, or to compensation for a pre-existing
respiratory acidosis (ie compensated chronic respiratory acidosis).
anion gap General: - The term anion gap (AG) represents the
concentration of all the unmeasured anions in the plasma. The
negatively charged proteins account for about 10% of plasma anions
and make up the majority of the unmeasured anion represented by the
anion gap under normal circumstances. - the AG = [Na+] + [K+] -
[Cl-] - [HCO3-] and a the upper range of normal is about 15 Major
Clinical Uses of the Anion Gap (i) To signal the presence of a
metabolic acidosis and confirm other findings - If the AG is
greater than 30 mmol/l, than it invariably means that a metabolic
acidosis is present. If the AG is in the range 20 to 29 mmol/l,
than about one third of these patients will not have a metabolic
acidosis. (ii) Help differentiate between causes of a metabolic
acidosis: -high anion gap versus normal anion gap metabolic
acidosis. The effect of albumin & phosphate - Albumin is the
major unmeasured anion and contributes almost the whole of the
value of the anion gap. - Every one gram decrease in albumin will
decrease anion gap by 2.5 to 3 mmoles. A normally high anion gap
acidosis in a patient with hypoalbuminaemia may appear as a normal
anion gap acidosis. - This is particularly relevant in Intensive
Care patients where lower albumin levels are common. - the 'normal
anion gap depends on the serum phosphate and the serum albumin.
anion gap = 0.2 x [albumin] (g/L) + 1.5 x [phosphate] (mmol/L)
metabolic acidosis with increased anion gap: Methanol, metformin
Uraemia DKA Phenformin, paraldehyde, propylene glycol, pyroglutamic
acidosis Iron, isoniazid Lactic acidosis Ethanol ketoacidosis,
ethylene glycol Salicylates, starvation ketoacidosis, solvent
metabolic acidosis with normal anion gap: Ureteroenterostomy (K+
decreased) Small bowel fistula (K+ decreased) Extra chloride (K+
increased) Diarrhoea (K+ decreased) Carbonic anhydrase (K+
decreased) Renal tubular acidosis (K+ decreased - type 1) Addison's
disease (K+ increased) Pancreatic fistula (K+ decreased)
13. adjunctive respiratory therapies general - Most critically
ill patients are unable to effectively clear secretions that
accumulate in the central and peripheral airways. This can be due
to factors such as: (i) increased secretion production, (ii)
impaired cough reflex, (iii) weakness, and (iv) pain. - Adjunctive
respiratory therapy addresses many of these concerns to prevent and
treat respiratory complications that are encountered in the
critically ill patient. general techniques methods to improve
mucociliary clearance 1. Percussion: - percussion of the chest can
aid in secretion clearance. - It is performed by clapping cupped
hands over regions of the thorax that are affected in a rhythmic
fashion or using mechanical devices that mimic the same action. 2.
High-frequency chest compression (HFCC): - relies on rapid pressure
changes to the respiratory system during expiration to enhance
movement of mucus in the peripheral airways to the central airways
for clearance. This method employs a vest worn by the patient that
is attached to an air-pulse generator. It is difficult to apply
this technique to most critically ill patients because the size of
the vest covering the thorax may prevent adequate monitoring. 3.
Manual hyperinflation - Typically, the lungs are inflated slowly to
one and one-half to two times the tidal volume or peak airway
pressures of 40 cm H2O as measured by a manometer. - It is held at
end inspiration with an inspiratory pause to allow for filling of
alveoli with slow time constants. - The goal of manual
hyperinflation is to recruit atelectatic lung regions to improve
oxygenation and improve clearance of secretions. -
Contraindications include hemodynamic compromise and high
intracranial pressure. - There is also a risk of barotrauma because
of preferential inflation of open lung regions that are highly
compliant compared with collapsed regions. 4. Positioning &
mobilization: - Mobilization of patients in the ICU either through
active or passive limb exercises may improve overall patient
well-being and in the long term may lead to better patient
outcomes. - Positioning also plays an important role. Position of
the patient with the head of the bed elevated at least 30 degrees
significantly reduces the risk of aspiration and ventilator-
associated pneumonia. - Positioning of selected individuals with
unilateral lung disease on their side with the affected side up can
lead to improved ventilation-perfusion matching (by gravitational
increased perfusion to the dependent "good" side). - If atelectasis
secondary to retained secretions is the cause, having the affected
side up leads to postural drainage. 5. tracheal suction - Used in
conjunction with other techniques to mobilize secretions from the
peripheral airways to the central airways, suctioning is an
effective way of removing secretions to improve bronchial hygiene.
- Because of the anatomic arrangement of the large central airways,
the suction catheter most often enters the right mainstem bronchus
compared with the left mainstem bronchus. - Complications with
suctioning include hypoxemia, especially in the setting of a
ventilator disconnect, increased intracranial pressure with
vigorous stimulation of the airways, mechanical trauma to the
trachea, and bacterial contamination. - All patients should be
preoxygenated with 100% oxygen for 1 to 2 minutes before
suctioning. - To reduce the risk of agitation, the patient should
be informed before tracheal suctioning is performed. The suctioning
should be limited to 15 to 20 seconds. The suction port on the
catheter should be opened and closed intermittently and not closed
for more than 5 seconds at a time. 6. Continuous rotational therapy
- extends the practice of regular 2 hourly repositioning of
patients from one side to the other by placing the patient on a bed
that moves to pre-programmed angles on a more frequent basis or
through the use of air mattresses that deflate alternatively from
side to side to provide the continuous postural position changes. -
Most studies on various patient populations demonstrate a lower
incidence of nosocomial pneumonia or atelectasis but no overall
improvement in other clinically significant outcomes such as
duration of mechanical ventilation, length of stay in the ICU, or
mortality. 7. Assisted coughing - Techniques include "huffing" in
the setting of an open glottis where in expiration the patient
forcibly exhales quickly several times. Other maneuvers include
abdominal or thoracic compression on expiration to generate high
intrathoracic pressures mimicking a cough. 8. Positive expiratory
pressure therapy (PEP) - involves the use of a facemask or
mouthpiece that provides a resistance to airflow of 10 to 20 cm H2O
on expiration. After repeating this maneuver a number of times,
mucus in the peripheral airways is mobilized and moved toward the
larger airways to be coughed or expelled with other techniques. 9.
Bronchoscopy - Fiberoptic bronchoscopy has the advantage of
providing direct visualization of the airways and permits
suctioning of specific segments where secretions may be retained,
causing problems such as atelectasis. - Bronchoscopy can be
considered as an adjunctive therapy for the treatment of
atelectasis or removal of secretions. - Being an invasive
procedure, bronchoscopy is not without risks, including
complications associated with sedation required for the procedure,
transient increases in ICP, hypoxemia, and hemodynamic
consequences/arrhythmias. methods to improve lung expansion -
Atelectasis is a common complication encountered in the critically
ill patient. This is often secondary to prolonged supine body
position and retained secretions obstructing airways. - Lung
expansion techniques mimic normal sigh maneuvers to help reverse
and prevent atelectasis and include: (i) Deep breathing and
incentive spirometry (ii) Intermittent positive-pressure breathing
aerosol therapies general: - The aerosolization of medications is
an effective method for drug delivery directly to lungs. The two
most common methods of delivery are via nebulization or via
metered- dose inhalers (MDIs). - The theoretical advantage of this
form of therapy includes direct delivery and activity at the site
of pathology and the ability to deliver high concentrations with
minimal systemic absorption and toxicity. - The most common
aerosolized therapy is the administration of bronchodilators. Other
medications that can be administered directly to the lungs include
corticosteroids, antibiotics, antifungal agents, surfactant,
mucolytic agents, and saline. (i) Nebulization: - the process of
using a high flow of gas (usually 6 to 8 L/min) to produce small
respirable particles of the liquid medium containing the medication
of interest. - in the spontaneously breathing patient approximately
10% reaches the lower respiratory tract/small airways. In
mechanically ventilated patients, 1% to 15% is delivered to the
lower respiratory tract. (ii) MDIs - pressurized canisters with the
drug suspended in a mix of propellants, preservatives, and
surfactants. - Factors that influence the efficacy of aerosol
delivery in the mechanically ventilated patient include: 1.
Position of administration in the circuit: the MDI should be closer
to the endotracheal tube at the Y-piece with a chamber, compared
with a pneumatic nebulizer, which should be at least 30 cm from the
Y-piece. 2. Humidification: this can decrease aerosol delivery to
the respiratory tract because of greater deposition in the
ventilator circuit. Higher doses may be required to achieve the
desired effect. 3. Timing of delivery: the aerosol should be
delivered during the inspiratory phase to maximize drug delivery.
4. Flow rates: slower inspiratory flow rates (and therefore longer
inspiratory time) increase delivery of nebulized medications. A
decelerating flow pattern can also increase delivery to the lower
airways. 5. Tidal volumes: larger tidal volumes greater than 500 mL
ensure optimal delivery. 6. Endotracheal tube size: tube sizes less
than 7.0 mm reduce delivery. 7. Density of inhaled gas: low-density
gases such as helium-oxygen mixtures increase deposition to the
lower airways by increasing laminar flow and producing smaller
respirable particle size. Bronchodilators: - Bronchodilators are
the most frequently administered aerosolized therapy in the
critically ill patient and are generally well tolerated in the
critically ill patient. - In mechanically ventilated patients, the
use of nebulization is either equally as good as or less effective
than an MDI with a spacer. MDI administration has the advantage of
easier use without the risk of bacterial contamination and need for
adjustment of flow rates. Antibiotics - Theoretical advantages of
aerosolized antibiotics include direct therapy at the site of
infection at higher concentrations with a lower risk of systemic
absorption and side effects. - The role for aerosolized or
instilled (via the endotracheal tube) antibiotics as an adjuvant
for the prevention or treatment of pulmonary infections in the ICU
remains to be defined with better clinical studies. Mucoactive
agents: - Induce bronchospasm and probably have no role Adrenaline:
- Racemic epinephrine has been used as a therapy for acute upper
airway obstruction secondary to inflammation
14. adjunctive therapies to improve oxygenation &
ventilation properties of NO clinical trials of NO - Numerous
clinical observational studies in ALI/ARDS have demonstrated
improvements in oxygenation by improving VQ mismatch as
demonstrated by a 10% to 20% increase in PaO2/FIO2 ratio and a
reduction on pulmonary vascular resistance and mean pulmonary
arterial pressures by at least 5 to 8 mm Hg. - Nitric oxide was
first described as a vascular-derived relaxing factor that caused
vasodilation via vascular smooth muscle relaxation. It is a highly
lipid-soluble gas that allows for rapid diffusion through the
alveoli-blood barrier into the pulmonary circulation and smooth
muscle cells of the vasculature. - The main action of NO is
mediated by activating guanylate cyclase and increasing
intracellular cyclic guanylate monophosphate, thereby causing
smooth muscle and subsequent vasomotor relaxation. - The beneficial
effects observed with inhaled NO are mediated primarily through
this action on the pulmonary vascular smooth muscle. Pulmonary
blood flow is specifically increased in well-ventilated regions,
which improves matching of perfusion to ventilation. - It also has
anti-inflammatory effects - Randomized controlled trials of varying
sample size and design had similar findings. Typically, NO improved
the PaO2 and PaO2/FIO2 ratios acutely, but by 24 to 72 hours those
in the control group achieved the same level of improvement. -
Similarly, although a reduction in mean pulmonary artery pressure
was also observed in these trials with the use of NO, this did not
translate into clinically meaningful outcomes of a decrease in
mortality, less organ failure, or days free of mechanical
ventilation. - Only 60% of ALI/ARDS patients respond to inhaled NO.
No clear predictors of who will respond to NO exist. clinical use
of nitric oxide - Given that doses below 40 ppm were safe without
any significant adverse effects, it can be considered a "rescue"
therapy to possibly allow for more protective forms of ventilation
with decreases in FIO2 and mean airway pressures to maintain
acceptable oxygenation or in situations in which secondary
pulmonary hypertension leads to compromised hemodynamic function
from right ventricular failure potential indications include: -
Inhaled NO is typically started at low doses ranging from 1 to 2
ppm and gradually increased until the desired effect is achieved. -
One method, as recommended from the U.K. Consensus conference on NO
use, is to perform a dose response test starting at 20 ppm and
reducing the doses to 10, 5, and 0 ppm to find the lowest effective
dose. A significant response should be considered as a 20% increase
in the PaO2/FIO2 ratio or at least a 5 mm Hg decrease in the mean
pulmonary artery pressure. - The improvement in gas exchange is
usually seen at lower doses. The dose required to reduce mean
pulmonary artery pressure is usually higher. The usual dose ranges
from 10 to 40 ppm. - Doses greater than 80 ppm are associated with
a higher risk for adverse effects. adverse effects of nitric oxide
- Adverse effects of NO include: (i) the formation of methemoglobin
and (ii) the spontaneous oxidation to nitrogen dioxide (NO2). NO2
is known to be toxic to the respiratory system with maximal
exposure limited to 5 ppm. Complications from NO2 exposure include
airway irritation and hyperreactivity with levels as low as 1.5
ppm, pulmonary edema, and pulmonary fibrosis when exposed to higher
levels. (iii) Rebound pulmonary: vasoconstriction can occur with
sudden discontinuation leading to rapid worsening of VQ mismatch
and pulmonary hypertension with significant hemodynamic collapse
safe administration of nitric oxide - To reduce the risk of
exposure to NO2, NO should be stored at concentrations no higher
than 1000 ppm in a pure nitrogen environment and only exposed to
oxygen at the time of administration. - NO should be delivered into
the ventilator circuit as close to the patient as possible. - NO
and NO2 levels should be monitored closely on the inspiratory side
of the Y-piece when using doses greater than 2 ppm.
contraindications to nitric oxide - An absolute contraindication to
NO therapy is methemoglobinemia reductase deficiency (congenital or
acquired). - Relative contraindications include bleeding diathesis
(secondary to reports of alteration in platelet function and
bleeding time with inhaled NO), intracranial hemorrhage, and severe
left ventricular failure (New York Heart Association grade III or
IV). inhaled prostaglandins - Inhaled prostaglandins I2 (PGI2) and
E1 (PGE1) are alternative medications that have effects similar to
inhaled nitric oxide with minimal systemic effects. - For PGI2,
doses ranging from 1 to 25 ng/kg/min are favorably tolerated with
similar reductions in pulmonary artery pressures and improvements
in oxygenation as inhaled NO. - PGE1 has the advantage of a more
rapid degradation by the pulmonary endothelial cells, providing a
selective advantage over PGI2 at higher doses. - Additional studies
are required to define a role for these agents, but they can be
considered as alternatives for rescue therapy for similar
conditions treated with inhaled NO. heliox - Helium is an inert gas
with a significantly lower density than room air (1.42 g/L for
oxygen versus 0.17 g/L for helium). - By substituting helium for
nitrogen in a helium-oxygen mix (heliox), the degree of reduction
in density of the gas is directly proportional to the fraction of
the inspired helium concentration in the mix. - Heliox reduces the
Reynolds number and thereby results in more laminar flow, therefore
reducing airflow resistance, work of breathing, and dynamic
hyperinflation associated with a high resistance. - Clinical
situations in which heliox may be used include conditions with high
airflow resistance such as severe acute exacerbations of asthma or
COPD, bronchiolitis, bronchopulmonary dysplasia, and extrathoracic
or tracheal obstruction. - Disadvantages of using heliox in
critically ill patients include the cost of therapy and the high
concentrations of helium required. Most studies utilize
helium:oxygen mixes of 80:20 or 70:30 to achieve a therapeutic
benefit. At higher concentrations of oxygen, the effect of helium
is less and therefore is limited in use to those not requiring high
FIO2. Ventilators also require recalibration for measured FIO2,
flows, and tidal volumes when using heliox.
15. adrenal insufficiency in sepsis & septic shock [created
by Paul Young 10/12/07] guidelines - international guidelines
recommend the use of low dose corticosteroids for the treatment of
septic shock. However, there are some discrepancies in these
recommendations. (i) the Surviving Sepsis Campaign recommended the
use of stress dose of corticosteroids for septic shock regardless
of adrenal function. (ii) the American College of Critical Care
Medicine Task Force recommended that stress dose of corticosteroids
should be used only in refractory septic shock or in adrenal
insufficient patients. mechanisms of action of corticosteroids
genomic actions - Cells from most tissues are responsive to
corticosteroids, which freely cross cell membranes. The
glucocorticoids receptor forms an inactive intracytosolic complex
with chaperone proteins like heat shock protein (HSP) 40, HSP56,
HSP70, and HSP90, immunophillins, P23, and other unknown proteins -
The receptor contains three domains: one binds corticosteroids, one
binds to DNA, also involved in dimerization; and one activates the
promoters within the genes. - Binding of corticosteroids to the
glucocorticoids receptor induces the release of chaperone proteins
and the dimerization of the complex, which then, enters into the
nucleus and interacts with specific binding sequences, the
glucocorticoid responsive element (GRE). - Subsequently,
transcription of some genes (e.g.most cytokines, adhesionmolecules,
lipoxygenase, etc.) initiated by various transcriptional factors
such as AP1, NF-AT and NF-kB are prevented. In addition,
glucocorticoids receptor dimers induce the inhibitor of NFkB (IkB).
- Other GRE sites upregulate the transcription of numerous other
genes (e.g. lipocortin-1, thymosin-b4 sulfoxide). Nongenomic
interactions - Physicochemical interactions occur in-between the
cell's membrane and corticosteroids inducing very rapid (within
seconds), nonspecific, nongenomic effects. - Some of these effects
might be part of the host response to sepsis. For example, loss in
the corticosteroids physicochemical interaction with hypothalamic
synaptosomes], may partly explain the loss in circadian rhythm of
cortisol synthesis during sepsis. - non genomic effects of cortisol
are thought to control immediate catecholamine release from
sympathetic cells. Such neural modulation by corticosteroids may
explain the rapid restoration of sympathetic modulation on heart
and vessels, and may account for the hydrocortisone induced rapid
pressure sensitization to exogenous catecholamine in septic shock.
corticosteroid induced immune modulation - by interacting with
NF-IL6, corticosteroids enhance the synthesis of the acute phase
reactants; with AP-1 and NF-kB, they inhibit the synthesis of
various proinflammatory factors. - corticosteroids prevent the
migration of inflammatory cells from circulation to tissues by
blocking the synthesis of various chemokines and chemotactic
cytokines. They prevent the synthesis of almost all proinflammatory
cytokines including several interleukins (interleukin-1,
interleukin-2, interleukin-3, interleukin-6), interferon-g (IFN-
g), granulocyte macrophage colony stimulating factor, and tumor
necrosis factor-a (TNF- a). They also enhance the production of the
macrophage migration inhibitory factor (MIF). - by stimulating the
synthesis of lipocortin-1, corticosteroids inhibit the synthesis of
soluble phospholipase A2 (PLA2) and the subsequent arachidonic acid
cascade, reducing the production of leukotrienes, the main
inflammatory mediators in humans. - corticosteroids also inhibit
the synthesis of inducible cyclooxygenase-2 (COX2) and of inducible
but not constitutive nitric oxide synthase (NOS). corticosteroid
induced cardiovascular modulation - Chronic corticosteroid excess
induces hypertension, whereas adrenal insufficiency induces
hypotension. - corticosteroids regulate vascular responses to
norepinephrine and angiotensin II, but not to vasopressin. The
underlying mechanisms remained unclear, and may involve multiple
pathways like iNOS and COX-2 inhibitions or the stimulation of the
phosphoinositide system. human studies - in healthy volunteers, a
6-hour infusion of 3 mg/kg/min hydrocortisone, either immediately
before or concomitantly to endotoxin exposure, prevented
LPS-induced fever, tachycardia, increase in plasma levels of
epinephrine, CRP, and TNF-a, but not interleukin-6. conclusion - In
septic shock, intravenous hydrocortisone (about 300 mg for 5 days)
decreases core temperature, heart rate, and plasma levels of PLA2
and C-reactive protein. - In a French multicenter trial on low dose
corticosteroids in septic shock, it was shown that the systemic
inflammatory response to sepsis, assessed by interleukin-6 levels,
was significantly altered by corticosteroids only in adrenal
insufficient patients - nonresponders (increment in cortisol of 9
mg/dl or less) to 250 mg of corticotropin. In that study, the
adrenal insufficient septic shock had higher TNFa, interleukin-6
and interleukin-8 levels than the remainders. - In another
placebo-controlled, randomized trial, 41 patients with septic shock
received 50mg bolus followed by a continuous infusion of 0.18
mg/kg/h of hydrocortisone until shock reversal. In that study, as
compared with the placebo, interleukin-6 levels were also
significantly decreased by hydrocortisone infusion, whereas
interleukin-10 levels remained unaltered. - low dose of
hydrocortisone has been shown to downregulate sepsis-associated
overexpression of the 'late' inflammatory mediator, MIF by
peripheral blood monocytes - In a recent randomized study, the
acute vascular effects of hydrocortisone (200 mg intra-arterial
over 3 hours) were investigated in healthy adult male volunteers.
This study elegantly demonstrated that hydrocortisone did not
affect biochemical or physiologic markers of nitric oxide activity.
Thus, one can conclude that any early (within 3 h) vascular effect
of hydrocortisone is not mediated through the NO pathway. - In
septic shock, several placebo-controlled randomized studies have
reported the cardiovascular effects of low dose of corticosteroids
(about 200-300 mg/day) given for a prolonged period. These studies
consistently showed that corticosteroids increased systemic
vascular resistance with little effects on the cardiac index and
pulmonary hemodynamics. - trials consistently show that
corticosteroids reduce the duration of shock. The probability of
being weaned from vasopressor at one week was greater in
corticosteroid- treated septic shock than in placebo-treated septic
shock and the relative risk was 1.60 - Only three trials have
subgroup analyses based on adrenal insufficiency. However, only two
studies used the same definition for adrenal insufficiency. In both
of them, the favorable effects of corticosteroids on shock reversal
were observed only in the adrenal insufficient patients
(nonresponders to corticotropin). - In the first study of 300
patients with septic shock, the median time to weaning from
vasopressors was reduced by 3 days in the corticosteroid-treated
adrenal insufficient patients compared with the placebo group (P =
0.001), while there were no difference between corticosteroids and
placebo in the responders to corticotropin. In the second study,
hydrocortisone significantly shortened the duration of shock (P =
0.02). This effect was seen only in the adrenal insufficient septic
shock (n=26; P=0.06), and not in the responders to corticotropin (n
= 15; P = 0.90). - Confalonieri et al. have investigated the
efficacy and safety of a 7-day treatment with intravenous
hydrocortisone (240 mg/day) in community-acquired pneumonia
associated sepsis. In their study, treatment with hydrocortisone
significantly prevented onset of shock (P =0.001), reduced multiple
organ dysfunction score (P =0.003), hospital length of stay (P =
0.03), and in-hospital mortality (P = 0.009). - In septic shock,
evidence from five randomized trials suggested that prolonged
treatment with low dose corticosteroids reduced 28-day mortality
(relative risk = 0.80, 95% confidence interval 0.67-0.95),
in-hospital mortality (relative risk = 0.83, 95% confidence
interval 0.71-0.97), and ICU mortality (relative risk = 0.83, 95%
confidence interval 0.70-0.97). It is important, however, to note
that one study accounted for 70% of patients included in that
meta-analysis. In this study, corticosteroids improved survival
only in adrenal insufficient septic shock. - In a meta-analysis of
all published randomized trials that evaluated the effects of high
or low doses of corticosteroids for short or long periods of time,
there was no evidence for significant increases of super-infection,
gastroduodenal bleeding, or hyperglycemia. - Corticosteroids could
be a valuable treatment for septic shock, depending upon the way
they are used. - There is no evidence to support the use of short
courses of high doses of corticosteroids in patients with severe
sepsis. - Current evidence suggests that, in septic shock, one-week
treatment with 200-300 mg of hydrocortisone alleviates the symptoms
of systemic inflammatory response, reduces the duration of shock,
and increases survival. Corticosteroids favorable effects on
inflammation, hemodynamics, and survival are more marked in
patients with an increment in cortisol of 9 mg/dl or less after 250
mg of corticotrophin (nonresponders or adrenal insufficient).
16. adrenocortical insufficiency [created by Paul Young
03/12/07] aetiology diagnosis of acute adrenal crisis physiology -
The adrenal gland is a mixture of the steroid hormone-producing
adrenal cortex and the adrenal medulla, which is responsible for
the secretion of catecholamines. - The secretion of cortisol and
aldosterone is controlled by different mechanisms, whereby the
pituitary axis (corticotropin-releasing hormone [CRH] or
corticotropin) is vital for cortisol secretion and the
renin-angiotensin system is vital for aldosterone secretion. -
Cortisol regulates a wide variety of genes involved in energy
metabolism (eg, glucose-protein-fatty acid metabolism), mineral
homeostasis, and immune function and influences many more cellular
functions. - Aldosterone has a more focused action on mineral
homeostasis - Although adrenal insufficiency has been known as a
clinical syndrome for a long time, new risk groups have been
identified, because as many as 20% of AIDS patients eventually
develop adrenal insufficiency. Moreover, patients with head trauma
develop pituitary insufficiency much more frequently than
previously recognized. symptoms of adrenal insufficiency
epidemiology - Primary and secondary adrenal insufficiency
(excluding critical illness adrenal insufficiency and adrenal
insufficiency secondary to acute interruption of chronic
glucocorticoid therapy) are rare diseases, affecting less than 0.1%
of the population - usually present slowly over time with
nonspecific symptoms of chronic fatigue, weakness and lethargy,
anorexia and weight loss, postural hypotension, abdominal
complaints (eg, nausea, vomiting, diffuse abdominal pain), and loss
of libido as well as loss of axillary and pubic hair in women. -
Hyperpigmentation (attributable to excess proopiomelanocortin and
melanocyte- stimulating hormone), especially of
non-sunlight-exposed skin areas, is an imported clinical hallmark
for the attentive and suspicious physician. - Abnormal serum
electrolytes with low sodium, high potassium, and, occasionally,
hypercalcemia and fasting hypoglycemia, and especially this
combination are highly suspicious for adrenal insufficiency. -
Acute adrenal insufficiency (adrenal crisis) is mainly attributable
to mineralocorticoid deficiency; thus, the clinical presentation is
dominated by hypotension or hypotensive shock. treatment - If
adrenal insufficiency is confirmed or highly likely based on the
acute screening results, replacement therapy should be continued by
the intravenous or intramuscular route (at 150-300 mg/d for 2 to 3
days) until full clinical recovery. High dose cortisol replacement
has major mineralocorticoid effects therefore no additional
mineralo- corticoid therapy is needed in the acute phase. - The
150- to 300-mg/d replacement dose of hydrocortisone is frequently
considered to be a physiologic stress dosage. However, serum
cortisol levels measured after such so- called ''acute
replacement'' dosages exceed several times the maximal stress
cortisol levels found in healthy or even critically ill patients
thereby questioning the need for maintaining such high acute
emergency replacement dosages. - In contrast to the rather generous
replacement dosage used in emergency situations, the chronic
replacement dosage for patients with adrenal insufficiency should
be as low as possible with clear instructions for dosage
adjustments in case of stress or acute emergencies. - Detailed
information about and education of the patient and of his or her
family and a medical emergency alert card as well as appropriate
follow-up should be initiated. pathophysiology - adrenal
insufficiency is a hormone deficiency syndrome attributable to
primary adrenal diseases or caused by a wide variety of
pituitary-hypothalamic disorders. - if such diseases evolve
gradually over time, they rarely cause an abrupt-onset adrenal
insufficiency crisis, whereas acute destruction of the adrenal or
pituitary gland or acute interruption of glucocorticoid therapy is
more likely to cause an acute onset adrenal failure crisis. - there
is increasing attention to relative adrenal insufficiency in
patients with acute (nonadrenal or pituitary) critical illness.
Such patients still secrete cortisol (and corticotropin in the
early phases of critical illness) but less than expected during
acute stress, and the survival of such patients can be improved by
pharmacologic doses of glucocorticoids.