OBSTRUCTIVE SLEEP APNEA SYNDROME AND SLEEPLESS ANAESTHETIST!

 

Which is the most common form of apnea? Perhaps the most common apnea,which causes lot of physiological disturbances due to anatomical alteration of body size or tissues, leading to serious pathological changes in body systems, is Obstructive Sleep apnea.Obstructive sleep apnea syndrome occurs when there are repeated episodes of complete or partial blockage of the upper airway during sleep.

During  episodes of sleep apnea,the diaphragm and respiratory muscles including the accessory muscles work hard to overcome the obstruction and the passage of air through the obstructed airway causes noisy breathing or snoring..Thus instead of getting a sound sleep for the victim, he falls into a "SOUND" sleep disturbing his partner or others.Thus due to obstruction the patient gradually stops his respiration momentarily and breathing usually resumes with a loud gasp,snort,or body jerk.These episodes can interfere with sound sleep[1]The physiological and pathological changes occurring in internal organs are due to relative deficiency of oxygen and retention of carbon dioxide. There is accumulating evidence that OSA is being considered as an independent risk factor for hypertension,diabetes mellitus,cardiovascular diseases and stroke, leading to increased cardiometabolic morbidity and mortality.

Definition:  

An apnoea is defined as the complete cessation of airflow for at least 10 sec.There three types of apnoea found clinically are obstructive,central and mixed.The frequency of apnoeas and hypopnoeas hourly is used to assess the severity of the OSAHS and is called the apnoea/hypopnoea index (AHI) or the respiratory disturbance index (RDI)According to the American Academy of SleepMedicine  recommendations,OSA is defined with AHI>5, and it is classified as mild OSA with AHI of 5 to 15;moderate OSA with AHI of 16 to 30; and severe OSA with AHI > 30.[2]

Respiratory effort–related arousal (RERA) is an event characterized by increasing respiratory effort for 10 seconds or longer leading to an arousal from sleep but one that does not fulfill the criteria for a hypopnea or apnea. The criterion standard to measure RERAs is esophageal manometry[12]

Symptoms:

Adults:
    Snoring
    Daytime sleepiness or fatigue
    Headaches on awakening in the morning.
    Poor concentration,Loss of memory, Depression,or Mental irritability
    Dry mouth or sore throat upon awakening
    Night perspiration
    Restlessness during sleep
    Sexual dysfunction
    Sudden awakenings from sleep with a sensation of gasping or choking

  In Children
    Drooling and often choking
    Excessive perspiration at night
    In drawing of the ribs while inspiration
    Learning and behavioral disorders
    Poor attention sleepiness and poor school performance
    Snoring
    Teeth grinding
    Restlessness during sleep
    Pauses or absence, cheyne stokes pattern of breathing
    Unusual sleeping positions, such as sleeping on the hands and knees, or with the neck hyperextended.

Causes of obstruction:

In adults the causes for obstruction include thick or large necks.They may have a relatively smaller airway with edentulous soft tissues where patency is maintained by active contractions of pharyngeal dilators which are depressed with sleep, alcohol, or sedatives.Babies and small children may have sleep apnea that is caused by swollen tonsils or hypertrophy of the uvula and soft palate.A larger than average tongue can also block the airway in many people as well as a deviated septum in the nose.

Risk factors:  

Age: Prevalence is high in the middle aged reaching a plateau by around 60 years.[3].Older people with OSAS are found have increased fat deposition in parapharyngeal area, lengthening of the soft palate,and
changes in body structures surrounding the pharynx.
Sex: OSAS is more common in men than women.
Obesity: BMI >30,Neck circumference more than 44 cm.The upper airway obstruction during sleep is attributed to increasing adiposity around the pharynx and body. Central obesity has been associated with reduction in lung volume,which leads to a loss of caudal traction on the upper airway, and hence, an increase in pharyngeal collapsibility.[4]
Family history and genetic predisposition: More common in first degree relatives of those with OSAS.
Craniofacial anomalies:Congenital or acquired alterations in the upper airway have been identified as risk factors for developing OSAS.Trauma, congenital anomalies like pierre robins syndrome.
Smoking and alcohol consumption: Cigarette smoking and alcohol have been shown to be risk factors for OSAS.Smoking induced airway inflammation is thought to be the causative factor while alcohol relaxes upper airway dilator muscles, increases upper airway resistance and may induce OSA in susceptible subjects

Pathophysiology:

People with sleep apnoea have a smaller pharyngeal airway than do matched controls.Also there will be alteration in bony structure and soft tissue surrounding the lumen.Due to the anatomical compromise,OSAS patients are susceptible to pharyngeal collapse during sleep or anaesthesia.Patients with OSA have increased pharyngeal dilator muscle activity which keep the airway patent during awake.Healthy individuals experience a loss of upper airway muscle tone at sleep onset (alpha-theta transition in the electroencephalogram) and experience some degree of breathing instability, an individual reliant on muscle tone due to an anatomical vulnerability will be particularly susceptible to apnoea when the dilator effect of pharyngeal muscles are lost.[5]Although pharyngeal dilator muscle responsiveness is likely impaired during NREM and REM sleep[6], the genioglossus can respond to both sustained mechanoreceptive (negative pressure) and chemo receptive stimuli, particularly when combined stimuli are present[7] The physiological response to this effect is a raise in CO2 due to respiratory obstruction and raise in negative intrathoracic pressure.The intrathoracic pressure appears to be a potent stimulus for genioglossal activation  and maintaining airway patency.Elevated endexpiratory lung volume may lead to increased caudal traction on the diaphragm which may keep the airway stable and patent.

Thus the sequence is airway obstruction, hypoxia, increase CO2,increased EMG activity causing genioglossus and other pharyngeal muscle activation,negative intrathoracic pressure and chemoreceptor activation causing arousal.The pharyngeal muscle patency may be restored even before arousal.The mechanism of arousal is thought to be activation of parabranchial nucleus of pons due to neurohumoral activation by hypoxia and hypercarbia.A deeper stage of sleep, central nervous system depressants, prior sleep fragmentation, and the presence of obstructive sleep apnea (OSA) have been observed to increase the arousal threshold to airway occlusion.[8]

 

Systemic effects:

Neurobehavioral and social:  Excessive daytime sleepiness, impaired vigilance, mood disturbances, and cognitive dysfunctions are the features of OSAHS. The sleepiness may interfere with efficiency in work and may worsen interpersonal and social relationships. The sleepiness may be  dangerous when driving and causes increase in road traffic accidents or  injuries when operating machinery. Partners of patients with OSAS experience poor sleep,and will be the first one who takes the patient to a doctor for evaluation of his sleep disorder.[9]

Cardiovascular: The intermittent hypoxia, Chronic hypercarbia, frequent negative intrathoracic pressure variations,and sleep disturbance and arousals lead to increase in blood pressure and lead on to sustained hypertension via chronically heightened sympathetic nervous system activity and arterial baroreceptor dysfunction.Myocardial infarctions are also common.The cerebrovascular system is also affected making the patient prone for CVAs and intracranial hypertension.Cardiac arrhythmias and cor pulmonale are commoner in these patients.[9]

Diabetes mellitus: OSAS is an independent risk factor for development of  Diabetes,associated with insulin resistance,Obesity further increase the risk. Obesity associated changes in pharyngeal muscles may also contribute to OSAS.[9] 

Liver: Hepatic dysfunction marked by  raised liver enzymes,fatty liver and fibrosis are also associated with OSAS [9]

Perioperative and postoperative considerations:

Patients with OSAHS may have increased perioperative risks.There is frequent prevalence of undiagnosed obstructive sleep apnea.Loss of control over airway, inability to mask ventilate, difficulty in intubation, intraoperative hypoxemia,abnormal raise in ETCO2 causing arrhythmias, intraoperative hypertension etc. are the problems anaesthesiologists face.The patients should be taken to OT adequately fasted and after acid aspiration prophylaxis.Fastrach LMA and fiberoptic bronchoscope are ideal for intubation and must be kept ready.It is advised to control the ventilations to match preoperative SPO2 and ETCO2.Spontaneous ventilations with LMA may cause hypoventilation and hypercarbia due to high rate of metabolism and increased thoracic mass.Whenever possible regional anaesthetic techniques or nerve blocks may be tried..Pre operative CPAP may be continued intra operatively also and extubation should be done when neuromuscular block is completely reversed and once the patient is fully conscious,communicative and able to generate adequate tidal volume.Semi sitting position or ramped position may be used to aid extubation, and the ETT may be pulled over a bougie or exchange catheter. Post operative respiratory depression is common and repetitive apnea may occur if the patient is somnolent.Monitor ETCO2 and SPO2 post operatively and if needed RBS and ABG may be performed frequently.Caution should be exercised when prescribing narcotics for post operative pain relief.

Diagnosis:     

 1)A sleep test or polysomnogram( PSG): may be used for confirmation.Sleep testing is performed in a sleep lab and is supervised by a trained technologist. The test will measure various body functions, including:

    Air flow
    Blood oxygen levels
    Breathing patterns
    Electrical activity of the brain
    Eye movements
    Heart rate
    Muscle activity
For more information about polysomnography visit:  http://classes.kumc.edu/cahe/respcared/cybercas/sleepapnea/trenpoly.html

 

                                                          The plysomnograph, Ref:[10]

                                                               UARS: upper airway resistance syndrome

2)Nocturnal sleep pulse oximetry:  The oxygen desaturation index (ODI) measures the mean number of episodes of oxygen desaturation per estimated sleep hour and is sometimes used as a surrogate for the
AHI.
3)Epworth sleepiness scale (ESS):  Used to measure excessive day time sleepiness[10].

Treatment:

1) Continuous positive airway pressure: 
Continuous positive airway pressure:(CPAP) is the preferred treatment of choice for OSAHS.[9] The required CPAP is titrated to a level that eliminates snoring, usually 5–20 cm Hg. A randomized placebo-controlled trial showed that CPAP can improve breathing during sleep, sleep quality, blood pressure,vigilance, cognition, and driving ability as well as mood and quality of life in patients with OSAHS.The drug Modafinil is found to be effective in treating OSAS along with CPAP.It was also observed that CPAP therapy improves hypertension usually by about 10mmHg.[11]

2) Mandibular repositioning splint:

Mandibular repositioning splints (MRSs)or oral devices work by holding lower jaw and the tongue forward, thereby increasing the pharyngeal airway.

3) Surgery:

Bariatric surgery is useful and often curative in patients with morbid obesity. Tonsillectomy is highly effective in children. Tracheostomy carries high morbidity and  may be curative but rarely used.[9]. Jaw advancement surgery, especially maxilla-mandibular osteotomy, is effective in patients with retrognathia.Somnoplasty uses radiofrequency energy to tighten the soft palate at the back of the throat.
Nasal surgery may be considered for correction of nasal obstructions, such as a deviated septum.

Uvulopalatopharyngoplasty: A procedure that  increases the width of the airway at the throat by removing soft tissue in the back of the throat and palate.

 Mandibular/maxillary advancement surgery : The procedure involves surgically moving the jaw bone and face bones forward to make more room in the back of the throat, done in severe cases of OSAS and in patient with facial anomalies.
   

Ref:

1). http://www.webmd.com/sleep-disorders
2).AASM,Sleep 1999; 21 : 667-89.
3).Young T, Skatrud J. Peppard PE. Risk factors for obstructive sleep apnea in adults. JAMA 2004; 291 : 2013-6.
4).Schwartz AR, Patil SP, Laffan AM, Polotsky V, Schneider H,Smith PL. Obesity and obstructive sleep apnea – pathogenic mechanisms and therapeutic approaches. Proc Am Thorac Soc 2008; 5 : 185-92.
5). Pathophysiology & genetics of obstructive sleep apnoea,Lisa Campana, Danny J. Eckert, Sanjay R. Patel† & Atul Malhotra.Indian J Med Res 131, February 2010, pp 176-187
6).Shea S, Edwards J, White D. Effect of wake-sleep transitions and rapid eye movement sleep on pharyngeal muscle responseto negative pressure in humans. J Physiol 1999; 520 : 897-908.
7).Stanchina ML, Malhotra A, Fogel RB, Ayas N, Edwards JK,Schory K, et al. Genioglossus muscle responsiveness to chemical and mechanical stimuli during non-rapid eye movement sleep.
Am J Respir Crit Care Med 2002; 165 : 945-9.
8).Respiratory arousal from sleep: mechanisms and significance.Berry RB, Bleason, Department of Medicine, Long Beach VA Medical Center, CA, 90822, USA.Sleep1997 Aug;20(8):654-75.
9). GC Mbata and JC Chukwuka1,Obstructive Sleep Apnea Hypopnea Syndrome Ann Med Health Sci Res. 2012 Jan-Jun; 2(1): 74–77.
10).www.sbu.se/upload/Publikationer/Content0/1/somnapne_fulltext.pdf
11)Shiomi T, Sasanabe R, Ohtake K, et al. Cardiovascular complications,Obesity-induced hypertension and obesity heart failure accompanying obstructive sleep apnea. Journal of the Japanese Society of Internal Medicine. 2004;93(6):1114–1119.
12)http://emedicine.medscape.com/article/295807-overview
Image courtesy:
1.Image header :evelyngarone.wordpress.com 
2. Image on diagnostic criteria and pathophysiology from Advances in Diagnosis and Treatment of Sleep Apnea Syndrome in Japan JMAJ 52(4): 224–230, 2009,Toshiaki and Ryujiro. 
3.The multicolour circular flow chart..http://www.dentonsleepdisorderlab.com/obstructive-sleep-apnea.html

10 COMMON 'PROCEDURAL BASICS' ANAESTHESIOLOGISTS MAY OVERLOOK!

“To err is human;to forgive,divine.”Remembering the famous poetry quote[1] by Alexander Pope (1688-1744).This means any human can make a mistake,so we should try to forgive them, just as,God said to show divine mercy to sinners and forgive them.Apart from medication error and faulty techniques, anaesthesiologists rarely make serious mistakes and any such mistake,if done may jeopardize the patient's life.It is usual that anaesthesiologists forget to observe some basic procedural steps,which may lead to technical difficulties but usually the situation is overcome by timely intervention or by modifying the technique.Here are some situations, where an anaesthesiologist may encounter difficulties during his routine anaesthesia practise when they fail to observe the basics.

1)The importance of sniffing position with pillow under occiput:

The standard procedure for endotracheal intubation consists of keeping the head in sniffing position supported by pillow under head.  Successful tracheal intubation is achieved by obtaining a good glottic view,which requires alignment of three optical axes corresponding to the oral, pharyngeal and laryngeal planes. Extension at the atlanto occipital joint together with a head elevation( moderate head elevation 5–10 cm above the surgical table) keeps the perfect axis for an easy intubation[2]Infants may need a small towel roll under the "shoulders" to align the head.Obese patients [3]elevated head-up position or "ramp"position is used. In this position, the shoulders are elevated with several pads, the head and neck are extended, and the external auditory meatus is in line with the sternal notch.Most the difficult airways arise due to defective positioning.

          figure 1

                                                     figure 2

2)Bag and mask ventilation without oral airway and intubation without applying cricoid pressure.

One 9 year old boy with respiratory distress was admitted to A and E following ARDS due to severe sepsis.The child was conscious but drowsy and dropping saturation. The anaesthesiologist was called in for intubation and he continued with initial bag and mask ventilation to maintain the saturation while preparing for intubation.An airway was not used and the air pumped into his lungs negotiated its way to stomach due to partial airway obstruction. While he did laryngoscopy, due to gag reflex he regurgitated and immediately aspirated. Further attempts to maintain saturation following intubation were not successful. Drowsy semiconscious patients with weak gag reflex may tolerate oral airway and definitely tolerate nasal airway which helps to direct the air into the lungs following ambu bag ventilation.[4].The basic rule states application of cricoid pressure with head down position will prevent aspiration.(application of cricoid pressure and its effectiveness is questioned and many controversies exist, but was found very useful practically)


















3)Intubation using a bougie in difficult airway.
Grades 2 and 3 glottic view may be managed by intubation over a bougie.Following laryngoscopy insert bougie into the glottis and then "rail road"the ETT over the bougie.The basic rule here is "dont remove the laryngoscope before railroading". Once you remove the scope after inserting bougie the epiglottis and pharyngeal soft tissues may come their way between the ETT and the bougie and cause intubation failure.Ask the assistant to pass the ETT over the bougie while the anaesthetist keeps the epiglottis elevated with his laryngoscope with one hand and stabilising the bougie with the other hand.

4)Removal of a Laryngeal mask airway.
Patients on spontaneous ventilation under LMA anaesthesia,it is advisable to remove the LMA in deep anaesthetic plane itself.If you wait till the patient is fully conscious,chance of biting the airway tube by patient is high which leads to total airway occlusion and any attempt to remove an LMA in this situation can cause damage to the LMA, laryngospasm or regurgitation by pharyngeal stimulation[5].The ideal sequence of removing LMA seems....remove in deep plane then cut down gases,insert oral or nasal airway,keep mask, turn head to one side, allow patient to recover by inhaling 100% oxygen.

5)Treating laryngospasm during recovery.
The treatment should be immediate,prompt and aggressive[6].Delay in treating laryngospasm may lead to serious morbidity.IPPV with 100% to break off the spasm is widely followed as the first line of management but there should not be any delay in administering suxamethonium.The most feared complications are hypoxia and negative pressure pulmonary edema.

6)Exsanguinate before IVRA.
Complete exsanguination of the upper limb is advocated before IVRA.Failure of proper exsanguination leads venous oozing during the procedure causing unsatisfactory operating conditions.Poor diffusion of the drug leads to 'patchy" anaesthesia or total failure of anaesthesia.The use of an esmarch or similar bandage is stressed.

7)Extubating a difficult airway.There are many gadgets available to deal with a difficult airway.With the introduction of fastrach LMA and fiberoptic bronchoscope, the success rate of intubation is high.Following ICU admission or surgical procedure many anaesthesiologists fail to observe the basic rule "while extubating a difficult airway take the same precaution and keep ready the same gadgets you used to intubate the case, since extubation failure or post extubation complications may necessitate immediate reintubation". Always use a guide wire or bougie over which the ETT is pulled out (extubation over bougie)and observe the vocal cord behaviour during extubation.

8)Testing loss of resistance. While testing for loss of resistance during epidural anaesthesia always use saline instead of air to avoid complications like pneumocephalus[7], spinal cord and nerve root compression, retroperitoneal air, subcutaneous emphysema, and venous air embolism[8] Alternatively saline with an air bubble technique also seems to be appropriate.

                                                                      Performing the LOR by saline, from NYSORA

9)Nasal intubation in pediatrics. Extreme caution should be taken while performing a nasal intubation in pediatric age group and any difficulty in ventilation should alert the anaesthetist of possibility of occlusion of the tip of  ETT with a piece of adenoid tissue carried away in it. Any incidence of difficulty in ventilation, high airway pressure,abnormal tracing of capnogram or fall in saturation following nasal intubation in children,the anaesthetist should not hesitate to remove the ETT immediately and proceed with mask ventilation and oral intubation. Never attempt to overcome the resistance by forced ventilatory attempts or by passing catheters into ETT..[9][10]The obstruction by adenoid is usually distal to murphy's eye and other common causes for the obstruction are kinking of ETT and severe bronchospasm following intubation.

10)Uncover during PAC!The last but not the least, make a detailed physical examination during PAC.It was found on many occasions that gross physical deformities were overlooked by anaesthetists due to lack of proper exposure of body parts.Such deformities include pectus excavatum, pectus carinatum,scoliosis, thyroid swellings and other congenital abnormalities,.All these situations may lead to devastating intra operative complications.

Ref:
1)http://www.quotecounterquote.com/2010/12/to-err-is-human-to-forgive-divine.html
2)http://www.anesthesia-analgesia.org/content/early/2011/05/18/ANE.0b013e31821c7e9c.full.pdf
3)http://www.anesthesia-analgesia.org/content/102/5/1592.1.full
4)http://www.acep.org/Clinical---Practice-Management/Focus-On---Bag-Valve-Mask-Ventilation/
5)http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007082/pdf
6) http://www.respond2articles.com/ANA/forums/thread/1096.aspx
7)https://www.aana.com/newsandjournal/Documents/p449-453.pdf
8)http://www.ncbi.nlm.nih.gov/pubmed/9010941
9)http://www.cas.ca/English/Page/Files/657_1344758.pdf
10)http://www.thefreelibrary.com/Nasotracheal+tube+occlusion+from+adenoid+trauma.-a0188739844

POST DURAL PUNCTURE HEADACHE,A NEVER ENDING STORY!

“Toward the evening I was forced to take to bed and remained there for nine days, because all the manifestations recurred as soon as I got up. At midnight a violent headache set in that quickly became insupportable.” This was the first experience of spinal headache in the history and was experienced by the great August Bier in 1898,when he suffered severe headache after spinal anesthesia given to him  by his colleague,on his request.The headache follows any diagnostic or therapeutic procedure of the spinal or epidural space.


According to Carrie and Collins [1]  post dural puncture headache (PDPH) is "a headache occurring after dural puncture and has a significant effect on the patient's post operative well being i.e. headache which is not only postural but also continues for more than 24 hours at any level of intensity or so severe at any time that the patient is unable to maintain upright position.According to the International Headache Society, the criteria for PDPH [2] include a headache that develops less than seven days after a spinal puncture, occurs or worsens less than fifteen minutes after assuming the upright position, and improves less than thirty minutes in the recumbent position with at least one of the following (neck stiffness, tinnitus, hypacusia, photophobia, and nausea). The headache should disappear within fourteen days after a spinal puncture; if it persists, it is called a CSF fistula headache.The incidence[3] of PDPH is estimated to be between 30-50% following diagnostic or therapeutic lumbar puncture,0-5% following spinal anaesthesia and up to 81% following accidental dural puncture during epidural insertion in the pregnant woman.Other than spinal anaesthesia the procedures leading to PDPH include,diagnostic lumbar puncture( where a big sized needle is used) labour analgesia with accidental dural puncture and therapeutic epidural steroid injections.

Do the needle size and type matters? Of course, researchers of the past 100 years have found that there is a definite relationship between the incidence of  PDPH and needle size. Reducing the size of the spinal needle has made a significant impact on the incidence of post‐spinal headache. The incidence[4] is  approx 40% with a 22G needle; 25% with a 25G needle; 2%–12% with a 26G Quincke needle; and less than 2% with a 29G needle. With needles of 29G or smaller, the technical difficulties may lead onto a failure of the procedure and multiple attempts may be required causing multiple dural puncture which in fact increase the incidence.Pencil point whitacre needles are now preferred.If the needle bevel is oriented parallel to the nerve fibres during spinal anaesthesia the incidence can be lowered further.PDPH is rare in children owing to their low CSF pressure[5]

Characteristic features of head ache: Ninety per cent of headaches will occur within 3 days of the procedure,[6]and 66% start within the first 48 h.[7] Rarely, the headache develops between 5 and 14 days after the procedure.The head ache is commonly distributed over the frontal and occipital areas radiating to the neck and shoulders and sometimes the temporal, vertex and nuchal areas also may be affected.Neck stiffness may be present. The pain is exacerbated by movements of the head, standing position and relieved by supine position.Other symptoms include nausea,vertigo,tinnitus,visual disturbances and rarely cranial nerve palsies.The headache is usually relieved in seven days but cases were reported where it lasted upto 3 months.The cause for the head ache is CSF leak leading to intracranial hypotension

Diagnosis: Mainly by clinical features and history of possible dural puncture.Additionally a diagnostic CSF tap may show, a  low CSF opening pressure, minimally raised CSF protein, and a rise in CSF lymphocyte count.The  MRI may demonstrate diffuse dural enhancement, with evidence of a sagging brain or descent of the brain.[8] Cisternography or CT myelography may be used for diagnosing a CSF leak.Untreated cases may develop intracranial hematoma due to rupture of bridging veins following intracranial hypotension.

Treatment: 

1) Bed rest: No use at all [9] but along with other measures very effective in reducing headache.

2) Simple analgesics: Paracetamol and other NSAIDs for mild pain.

3) Posture: Supine position helps to maintain the CSF pressure and prone position increases intra abdominal pressure and  the CSF pressure and gives instantaneous relief. However prone position may not be comfortable for the patient.Supine position helps to avoid complications like intracranial hemorrhage and seizures due to low CSF pressure.

4) Abdominal binders: Should be tight enough to increase the intra abdominal pressure.

5) Caffeine : Caffeine is a CNS stimulant and cerebral vasoconstrictor.The recommended dose is 300-500 mg of oral caffeine once or twice in a day[10] [11]It is assumed that caffeine acts through vasoconstriction of dilated cerebral vessels.Caffeine is associated with some adverse events like cardiac arrhythmias and maternal seizures and necessary precaution may be taken. High doses of the drug may reach the baby through breast milk and can cause neonatal irritability[12]

6) Sumatriptan:  Sumatriptan is a 5‐HT_1D receptor agonist that promotes cerebral vasoconstriction,acts in a similar way to caffeine. It increases the cerebral vascular tone.

7) Synthetic ACTH: was first reported to be effective for treating PDPH in the 1990s. Postulated
mechanisms include CSF retention through increased mineralocorticoid mediated sodium reabsorption,
and a direct analgesic effect via its glucocorticoid activity[12]. A randomised controlled trial in 2004 found no effect of a single intramuscular injection of Synacthen compared with an intramuscular injection of normal saline.ACTH has been administered as an infusion [13] 1.5 microgram per kilogram. 

8) Desmopressin(DDAVP): injection intramuscularly  before spinal injection has also proven to be effective but more reasearch is required to prove its efficacy.

9)Adequate hydration:  was found to be helpful but overhydration must be avoided. 

10)Epidural Blood Patch: Perhaps the most effective treatment for PDPH is epidural blood patch(EBP).the concept of EBP has developed following the observation that bloody taps were associated with reduced incidence of headache.The first epidural blood patch was performed in 1960 by theAmerican  surgeon, Dr James Gormley.The mechanism is that once blood is introduced into the epidural space it coagulates and form a seal occluding the puncture site preventing further CSF leak.The procedure is associated with high success rate and low incidence of complications and has become the standard mode of treatment for PDPH.Before initiating the treatment one has to look for the contraindications like coagulopathy, local infections, fever or patient refusal.A sample of the patient's blood may be sent to lab for culture[14].If symptoms of PDPH persist after 24-48 hours,or the headache is disabling,consider an epidural blood patch. 

 Guidelines[15] for placement of epidural blood patch (St.George Hospital, London)

The procedure must be carried out in theatre. Two anaesthetists are required, one of whom should be a consultant.
1. Written, informed consent should be obtained from the woman following a careful explanation of the procedure. The discussion should also include the chances of success, significant side effects and the possibility of requiring a second blood patch(approximately 1 in 5).
2. The epidural space is located with a Tuohy needle, by the first anaesthetist, at the level of the supposed dural puncture, or an intervertebral space above or below. CSF may be present in the epidural space. 20 –  30 ml of the patient’s blood (provided by the second anaesthetist) is then injected into the epidural space over 30 – 60 seconds. Dull, lower back pain may limit the volume injected, although pausing for a few seconds or slowing the rate of injection may allow the full amount to be injected.
3. The second anaesthetist is responsible for drawing blood from the patient. As with the epidural, vene puncture must also be carried out using a full aseptic technique. After cleaning and draping the skin of the antecubital fossa, the skin should be anaesthetized with local anaesthetic prior to the insertion of a 14 or 16 gauge cannula. This should be done when the epidural needle is sited.
4. It has previously been thought that samples of the blood should routinely be sent for culture. This is an area of much controversy, and is backed up by little evidence,however until we have a definitive answer to this question it would seem prudent to continue to send blood for screening purposes. There is no evidence for the routine use of prophylactic antibiotics following blood patch.
5. The epidural blood patch should be carried out in the Obstetric theatre. Immediately following the procedure the patient should be taken to the recovery area for close observation. The patient is encouraged to lie still for one to two hours. After this time she can be transferred to the ward where she should be encouraged to walk.
6. It is important that the patient has repeated clinical assessment while an inpatient,although she may well go home the same day. Prior to going home, advice must be given regarding the need to contact labour ward or present to an Accident and Emergency department in the case of any complications. Specifically patients should be told about presenting features of cauda equina syndrome and epidural abscess.Where
possible written information should also be given. " During placing of EPB thus patient always should be asked about any acute occurrence of new pain, radiating pain and sharp shooting pain. Thus in EPB always a test dose of 2-3 ml of blood should be injected and patient should be evaluated. The total volume should be injected in increments of 2-3 mls".

 Mechanism of action of  EBP: After injection the patient should remain supine and immobile for
30 minutes to 2 hours to allow the blood to form a clot.Once injected the blood is distributed caudally and cephalad regardless of the direction of the bevel of the Tuohy needle. The blood also finds its distribution circumferentially around to the anterior epidural space. This has been proved [16] by using radiolabelled red cells or by MRI.There is evidence of  thecal space compression and escape of blood through the intervertebral foramina and into the paravertebral space.The injected blood spreads up about six spinal segments cephalad and three segments caudad.The procoagulat property of CSF accelerates clotting of blood and the puncture site is sealed followed by an immediate relief of headache.At 7–13 h, there is clot resolution leaving a thick layer of mature clot over the dorsal part of the thecal sac.[17]

Efficacy of blood patch: EBP is likely to be most effective if performed at least 24 hours after the onset of PDPH.The success rate varies between 75-90% and about 40% patients may need second EBP.The technique is safe and the rare transient complications include radiculopathy,backache, neckache and bradycardia.Major complications are rare,and may include meningitis, subdural haematoma, seizures, arachnoiditis, spastic paraparesis, dural puncture,cauda equina syndrome etc.If an epidural blood patch fails to relieve a PDPH, it is advisable to consider radiological imaging of the head to exclude other pathology prior to repeating the blood patch.

Prophylactic blood patch: The beautiful explanation in this regard is by Dr Nicola Jane Campbell FRCA, Effective management of post dural puncture headache  Anaesthesia tutorial of the week  181, 31st may 2010.He says,
A potentially attractive option in the face of a recognised dural puncture with a Tuohy needle is to resite the epidural so that a prophylactic epidural blood patch (PEBP) can be provided in the hope of preventing a subsequent PDPH. The popularity of this technique has diminished recently for a number of reasons including the limited evidence that PEBP reduces the requirement for a therapeutic EBP, the increasing use of intrathecal catheter placement following dural puncture which may itself reduce the risk of subsequent PDPH and the recognition that some dural punctures don’t result in a PDPH and many PDPHs do not require a therapeutic EBP. Administering a PEBP to patients following duralpuncture may therefore expose these patients to an unnecessary procedure with associated risks.
Epidural saline and Dextran: theoretically a suitable alternative to EBP and thought to be safe as they are sterile solutions.These techniques are very useful in Jehovah witnesses patients or patient with bacteremia and HIV infection .They increase the CSF pressure by mass effect but formation of a coagulum and subsequent sealing effect over the dura are doubtful.Regimens include (i) 1.0–1.5 litre of epidural Hartmanns solution over 24 h, starting on the first day after dural puncture;[18] (ii) up to 35 ml h^–1 of epidural saline or Hartmanns solution for 24–48 h, or after development of the headache; (iii) a single 30 ml bolus of epidural saline after development of headache;[19] and (iv) 10–120 ml of saline injected as a bolus via the caudal epidural space.The tamponade effect of epidural dextran is also transient and similar to saline offering no advantage over saline.In neither of these an aseptic inflammatory response over the dura was found.

Epidural Morphine: Administration of epidural morphine soon after inadvertent dural puncture as prophylactic measure to prevent PDPH has been advocated by  many authors but evidence lack due to absence of large controlled trials.

Fibrin glue: As an alternetive to blood patch fibrin glue injection into the epidural space was found to be helpful..The procedure may be done blindly or by CT guided percutaneous injection.The failure rates are high.  Chance of development of aseptic meningitis makes the procedure less acceptable to many. 

Intrathecal catheters:An alternative method of managing ADP by passing an epidural catheter through the needle into the subarachnoid space was described by Cohen in 1989. Since then, several studies have claimed a reduction in incidence of PDPH if the epidural catheter is inserted intrathecally at the time of dural puncture and removed after at least 24 h. Injection of a 10 ml bolus of normal saline into the intrathecal catheter before its removal further reduced the incidence of PDPH. [20]It was postulated that placement of
a spinal catheter through the perforation may provoke an inflammatory reaction that will seal the hole. However, neurological complications, such as cauda equina syndrome and infection, should preclude the use of intrathecal catheters and keeping the catheter for more than 24 hours is also not advocated

Surgical closure: Surgical closure of the dural perforation is the last resort to treatment

Preventing PDPH; Preventive measures like smaller needle size, shape of needles and direction of needle bevel in relation to dural fibers, should always be considered.For spinal blocks, pencil point needles of 25 G or smaller should be used, especially in the obstetric population.While performing Epidural anaesthesia Loss of resistance to saline performed with continuous pressure on the syringe plunger may have the effect of
moving the dura anteriorly as the needle approaches thereby reducing the likelihood of dural puncture
compared with an intermittent pressure technique with air.Other precautions should include ensuring an optimal patient position, slow controlled advancement of the needle and limiting patient movement during the procedure by using adequate local anaesthetic infiltration[12].When there is difficulty  use of ultrasound guidance for epidural placement may be considered.

Differential diagnoses: for PDPH:Tension Headache,Migraine Headache, Caffeine Withdrawal, Lactation Headache, Hypertension, Pneumocephaelus, Meningitis, Subarchnoid Heamorrahge, Spontaneous Intracranial Hypotension and eclampsia.

PDPH is the most distressing experience for post operative patient and can lead on to significant morbidity and death..Apart from increasing the duration of hospitalisation, it can cause  auditory and visual disturbances, nausea, vomiting ,cranial nerve palsy and intracranial hemorrhage due to low CSF pressure.The treatment should be aggressive with conservative methods initially and in severe and resistant cases with CNS involvement  EBP may be tried..Mostly the headache is benign and will be resolved spontaneously in 5-7 days

A current review about PDPH by Steve Schwalbe, MD is found to be interesting in this context..http://www.soap.org/media/newsletters/fall2000/pathophysiology_management.htm

Ref:
1) Carrie Less, Collins PD. 29 guage spinal needle. Br J Anesth 1991; 66 :145-6.
2) R. W. Evans, “Complications of lumbar puncture,” Neurologic Clinics, vol. 16, no. 1, pp. 83–105, 1998
3)http://www.frca.co.uk/Documents/181%20Post%20dural%20puncture%20headache.pdf
4) Barker P. Headache after dural puncture. Anaesthesia 1989; 44: 696–7
5) Carbajal R, Simon N, Olivier‐Martin M. Post‐lumbar puncture headache in children. Treatment with epidural autologous blood (blood patch). Arch Pediatr 1998; 5: 149–52
6) Reynolds F. Dural puncture and headache. Br Med J 1993; 306: 874–6
7) Leibold RA, Yealy DM, Coppola M, Cantees KK. Post‐dural‐puncture headache: characteristics, management, and prevention. Ann Emerg Med 1993; 22: 1863–70
8) Mokri B, Parisi JE, Scheithauer BW, Piepgras DG, Miller GM. Meningeal biopsy in intracranial hypotension: meningeal enhancement on MRI. Neurology 1995; 45: 1801–7
9) Spriggs DA, Burn DJ, French J, Cartlidge NE, Bates D. Is bed rest useful after diagnostic lumbar puncture? Postgrad Med J 1992; 68: 581–3
10) Sechzer PH. Post‐spinal anesthesia headache treated with caffeine. Evaluation with demand method. Part 2. Current Therapeutic Research, clinical and experimental 1979; 26: 440–8
11) http://www.update-software.com/BCP/WileyPDF/EN/CD007887.pdf
12) Dr Nicola Jane Campbell FRCA, Effective management of post dural puncture headache  Anaesthesia tutorial of the week  181, 31st may 2010
13) Collier BB. Treatment for post‐dural puncture headache. Br J Anaesth 1994; 72: 366–7
14)Crawford JS. Experiences with epidural blood patch. Anaesthesia 1980; 35: 513–15.
15) http://www.oaa-anaes.ac.uk/assets/_managed/editor/File/Guidelines/PDPH/PDPH_diagnosis_management%20PDPH_Wendler_StGeorges.pdf
16) Szeinfeld M, Ihmeidan IH, Moser MM, Machado R, Klose KJ, Serafini AN. Epidural blood patch: evaluation of the volume and spread of blood injected into the epidural space. Anesthesiology 1986; 64: 820–2
17) D.K.Turnbull,D.B, shepherd,Post dural puncture headache, pathogenesis, prevention and treatment Br J Anaesth 2003; 91: 718–29
18) Crawford JS. The prevention of headache consequent upon dural puncture. Br J Anaesth 1972; 44: 598–600
19) Moir DD. Recent advances in pain relief in childbirth. II: regional anaesthesia. Br J Anaesth 1971; 43: 849–57
20) http://www.joacc.com/article.asp?issn=2249-4472;year=2011;volume=1;issue=2;spage=57;epage=66;aulast=Nath

THE GOLDEN RULES OF ANAESTHESIA

Back to the basics!!! Safe conduct of anaesthesia should be the priority when surgical cases are posted for procedures.The expertise and experience of the anaesthetist along with proper monitoring are essential in achieving this goal, but without considering  the basics of anaesthesia practise even an experienced physician backed up by all essential monitors may turn to be a dangerous anaesthetist. Here are the ten golden rules of anaesthesia which stand immortal even in the midst of recent advances.

1.Assess and prepare the patient adequately:So that you will not anaesthetise anyone with multisystem disorders, heart disease,anemia or metabolic disorders.The physician should get sufficient information about the medications the patient is receiving as the drug interaction of these drugs with anaesthetic agents are complex and sometimes dangerous.Prepare the patient by correcting dehydration, severe anaemia,diabetes, heart failure,hyperthyroidism etc..Identifying pre existing diseases and correcting them help the anaesthetist for proper risk stratification of cases and a proper plan of anaesthesia technique can be made.The detailed explanation of the anaesthesia procedure must be offered to the patient and an informed consent must be obtained.

2.Starve the patient even for local anaesthesia: So that if the patient tries to vomit his stomach is less likely to be full. In case the local anaesthesia fails or a toxicity or CNS involvement by the local anaesthetics he may have to administer general anaesthesia or to resuscitate the patient.

3.Anaesthetise him on a tipping table: Because he may still vomit ,even if he is supposed to have been starved.So you must be able to tip him head down.If you do this, the chance of aspiration (even if he regurgitates)is very less.

4.Check your drugs and equipment: Before your start,especially if you are using less simple equipment. The equipment to preserve his airway must be ready beside you.All drugs including drugs for emergency use must be loaded and labelled.The anaesthesia machine and monitors should be checked as per routine checking protocols.

5.Keep a sucker instantly ready: Tested and working,so that if his pharynx fills with vomit,you can suck it out.You will also need suction catheters.A properly working suction catheter is mandatory for administering anaesthesia.

6.Keep airway clear:  Because it can be easily obstructed.One way to do this is to use a Guedel's airway.You will need a range of different sizes. Alternatively you can use the triple manuevour too. Recently with the introduction of LMAs the airway management has become simpler and easier.

7.If the patient needs ventilation: Have a self inflating bag, non re breathing valve,and a face mask ready.You may need to intubate the patient.Have access to laryngoscope, tracheal tubes,an introducer and suction catheters.Intubation is the only way you can be sure to control his airway and prevent aspiration.

8.Have a vein open:  Because if the patient has a drip,or an indwelling needle you can treat some of the complications ,that may arise during anaesthesia more easily, and give him both blood and fluids quickly.An open vein is an essential precaution in all major operations.

9.Monitor pulse and blood pressure: Continually during the operation and immediately after it,so that you are able to take the the necessary corrective action before it is too late.You must recognise cardiac arrest immediately.One of the most effective ways to do this is to strap a precordial stethescope to his chest and listen to the sounds.(we have advanced to the level of TEE now)

10.Always have someone in the room who can apply cricoid pressure: Some body who is experinced in giving cricoid pressure effectively must be available in the operating room.He should be either a second anaesthetist or a nurse anaesthetist.The practise is useful in emergency and to anaesthetise full stomach patients.Now the practise of cricoid pressure is a controversial issue as some physicians believe it will do more harm than good .They argue that the pharyngeal stimulation may result in  regurgitation and it is difficult to estimate the required pressure.Also placement of LMA is difficult and chance of tracheal cartilage injury is high.. 

These Golden rules were published in the beginning of anaesthesia practise aiming  to help the anaesthetist to deliver safe anaesthesia but many of the rules stated are applicable to modern days of practise as well..The anaesthesiologist should not forget the directive primum non nocere (“first of all do no harm”)  and should always observe the basics, guidelines and protocols in spite of advanced monitoring.Let us remember the saying 

‘Provide good care with very few monitors’

‘More monitoring, however does not necessarily lead to better care’

‘No monitor can ever replace a human being as he has the 6th sense.’

‘The focus of attention for greater part of the time should be on the patient and the operation, not on monitors.’

                                                                                      - Wendell C. Stevens

Ref: 1) Primary Anaesthesia Edited by Maurice King, Oxford University Press 1992

       2)http://books.google.co.in/books?id=rCvEJibQstcC&pg=PA22&lpg=PA46&ots=fsjiLMmdTp&dq=golden+rules+of+anaesthesia

ASA PHYSICAL STATUS CLASSIFICATION, NEEDS TO BE REVISED?

The American  Society of Anaesthesiology classification of  physical status(ASA) is still  used  widely as a scoring system to assess the fitness of  patients subjected to anaesthesia and surgery. The scoring  system was devised to assess the physical status of patients before anaesthesia is planned and was applied uniformly for all patients.The grading system was  useful for record  keeping and for statistical analysis of patients' health status who were scheduled for  administration of anaesthesia.This  grading system is not indicated  for prediction of operative risk.

The evolution of ASA  grading  system[1]

In 1940-41, ASA asked a committee of three physicians (Meyer Saklad, M.D., Emery Rovenstine, M.D., and Ivan Taylor, M.D.) to study, examine, experiment and devise a system for the collection and tabulation of statistical data in anaesthesia which could be applicable under any circumstances.[1] They were  given the  task to devise a grading system to assess the  operative risk , but  after  detailed studies  research and discussion they  stated that "In attempting to standardize and define what has heretofore been considered 'Operative Risk', it was found that the term ... could not be used. It was felt that for the purposes of  the anesthesia record and for any future evaluation of anesthetic agents or surgical procedures, it would be best to classify and grade the patient in relation to his physical status only."They described a six-point scale, ranging from a healthy patient (class 1) to one with an extreme systemic disorder that is an imminent threat to life (class 4). The first four points of their scale roughly correspond to today's ASA classes 1-4, which were first published in 1963.[2] The original authors included two classes that encompassed emergencies which otherwise would have been coded in either the first two classes (class 5) or the second two (class 6).Two modifications were made in 1963 when the new classification is proposed ,the previous classes 5 and 6 were removed and a new class 5 was added for moribund patients not expected to survive 24 hours,with or without surgery.In addition emergency cases were  designated  by the letter 'E'.[3] The sixth class is a recent addition for declared brain dead organ donors. The six ASA  classes  for evaluation of physical status are 

ASA I

An immediate  green flag: Normal healthy patients  are  coming under this group.Ptients can walk one flight of stairs or two level city blocks without distress.No clinical co morbidity , no significant  past or present medical or surgical history.
ASA II

Patients have mild to moderate systemic disease which is well controlled.Patients are able to walk up one flight of stairs or two level city blocks,but with  moderate levels of exertional distress. History of well-controlled disease states including non-insulin dependent diabetes,Patients with anginal symptoms less than once a week,High blood pressure  treated with a single type of medicine,[4],or asthma controlled by inhalers. ASA III

Patients with severe systemic disease that limits activity, but is not incapacitating.Angina symptoms more than once a week,Taking more than one blood pressure tablet Having complications of diabetes such as kidney failure or poor circulation,Asthma requiring frequent hospital admissions,Respiratory disease [COPD / COAD] causing breathlessness climbing a single flight of stairs,Someone with a raised creatinine of less than 200 micro mol/L,without dehydration, are all examples.[5]

ASA IV

A Patient with severe systemic disease that is a constant threat to life:Advanced liver disease, severe COPD, ARDS,  History of unstable angina pectoris, myocardial infarction or cerebrovascular accident within the last six months, severe congestive heart failure, , and uncontrolled diabetes, hypertension, epilepsy,etc.

ASA V

A moribund patient not expected to survive 24 hours with  or without surgery, eg;Severe  gangrenous intestine in septic shock or terminally ill patients.

ASA VI
A brain dead donor  for organ harvestation.

The prefix 'E' is added to emergency operation of any class eg; ASA I E, for  emergency  caesarean section in an ASA I patient.

The inconsistency and inadequacy of ASA grading system has been questioned for many years. The major drawbacks of  this grading system are

• Inconsistency of grading between anesthetists.[6],Research by Haynes, S. R. and Lawler, P. G. P, showed that  so much variation was observed between individual anaesthetist's assessments when describing common clinical problems and that the ASA grade alone cannot be considered to satisfactorily describe the physical status of a patient.
• Age; is not  considered as an influencing factor,extremes of age like elderly patients and neonates may have poor tolerance to surgery and anaesthesia in the absence of systemic illness and cannot be considered as ASA 1 patients.
• The grading system is not well suited for assesing physical status of special  clinical conditions like burns,trauma and metabolic disorders
• No grade was available to describe moderate systemic illness.
• The ASA Grading System shows poor interrater reliability in pediatric practice[7]

Here comes the importance of revising the ASA physical status system.An attempt was made by  Tomoaki Higashizawa M.D., Ph.D. and Yoshihisa Koga M.D.,who revised the score and introduced a 7 graded scoring system.This was done by modification of the original ASA grading system as below.[8] The authors claim reevaluation of ASA physical status (7-grade) can provide a better grading outcome for predicting the incidence of intra- and postoperative complications in surgical patients compared with the conventional ASA's.

With 2 subclasses 1a 1b,2a,2b this classification seems to be appropriate to fill up the gap between the severity of systemic illness  but difficult to apply for routine use because of its complex nature.We expect that a revision of ASA  grading system will be implemented soon by ASA.

Many anaesthetists are concerned more with the morbidity and mortality of associated risk conditions, The physical status evaluation alone was not useful for risk stratification and many other grading systems were devised to evaluate the perioperative risk.eg; E-PASS and POSSUM score.
Reference:

1)Saklad M. Grading of patients for surgical procedures. Anesthesiology 1941; 2:281-4.(by courtesy of WIKIPEDIA)
2) Little JP (1995). "Consistency of ASA grading". Anaesthesia 50 (7): 658–9. pubmed.
3)New classification of physical status. Anesthesiology 1963; 24:111
4)Margaret J. Fehrenbach, RDH, MS, from the American Society of Anesthesiologists, Medical Emergencies in the Dental Office (Malamed, Mosby, 2008), 
5)http://www.nhfd.co.uk/003/hipfractureR.nsf/ (National hip fracture database)
6)Haynes, S. R. and Lawler, P. G. P. (1995), An assessment of the consistency of ASA physical status classification allocation. Anaesthesia, 50: 195–199.
7)Aplin S, Baines D,Lima, Use of the ASA physical status grading system in pediatric practice.,Pediatric Anaesthesia,2007 Mar;17(3):216-22.
8)T. Higashizawa & Y. Koga : Modified ASA Physical Status (7 grades) May Be More Practical In Recent Use For Preoperative Risk Assessment . The Internet Journal of Anesthesiology. 2007 Volume 15 Number 1.

LOCAL ANAESTHETIC TOXICITY, WHAT INTRALIPID CAN OFFER?

A 30 year old ASA 1 patient weighing 70 kg  is scheduled for open reduction and internal fixation of fracture both bones on right upper limb. The pre anaesthetic check up was unremarkable except for mild nasal allergy.The patient received 3 mg intravenous midazolam in operation theatre for sedation and an interscalene brachial plexus block was attempted by the anaesthetist using 20 ml 1% lignocaine along with 20 ml 0.25% bupivacaine.Analgesia was adequate and  almost complete after 10 minutes of the block and the surgeon was about to operate. The patient complained of dizziness and vomited once.The blood pressure dropped below70 mm Hg systolic and the pulse was felt slow, feeble and thready. The chest on auscultation revealed equal and bilateral air entry.   Later on he complained of numbness of the face and began to convulse. Immediate support of airway and ventilation provided by mask ventilation and  intubation after intravenous thiopental.  Intravenous fluids administered  and intravenous ephedrine given at increments . Blood pressure dropped further down and patient  had a cardiac arrest following asystole. CPR  given as per ACLS protocols and a lipid emulsion was requested. The patient responded to resuscitative efforts and intralipid administration was not necessary. He was shifted to intensive care unit for close monitoring of vitals  and has fully recovered without any neurologic sequelae.

Local anaesthetics  are drugs used to prevent or relieve pain in specific regions of the body without producing unconsciousness. They  block pain sensation by blocking  conduction of pain impulses through nerves.Motor blockade and autonomic blockade are also observed as part of local anaesthetic action.Local anaesthetic drugs are widely used in dentistry and surgical specialities for providing surface anaesthesia, infiltrative anaesthesia or for nerve block. They are indispensable for the anaesthetist, in providing Regional Anaesthesia.The drug lignocaine find an unique place in crash cart for CPR and in emergency medicine trolley for treating arrhythmias.No pain management services can run without using local anaesthetics.However precaution must be taken while using them as chances of toxicity or side effects are high and may even be fatal. Manifestations of toxic reaction may range from minor urticaria or edema to very severe neurological toxcity or severe cardiovascular collapse.So basic resuscitation equipments and essential drugs should be kept ready before administering LAs to any patient. A brief review of local anaesthetic toxicity and its management, is given here.

 Pharmacology:  Structurally, all local anaesthetics are similar and consist of three parts: a lipiophilic (aromatic) end, a hydrophilic (amine) end, and a link between the two ends.[1] This intermediate link can be either an aminoester or an aminoamide bond, which classifies the local anaesthetics into two different groups: amides and esters. Esters include Procaine, Cocaine, Chlorprocaine, Amethocaine, etc .Amides include Lignocaine, Bupivacaine, Levobupivacaine, Ropivacaine etc.

 

All local anaesthetic drugs are weak bases  and exists in an equilibrium between ionised and non ionised forms in solution.The non-ionised form diffuses readily across the neuronal membranes into the axoplasm, where it ionises  and blocks sodium channels within the cell.

Factors affecting the anaesthetic activity of local anaesthetics include the dissociation constant (pKa),[2]
protein binding, lipid solubility, pH, and vascularity at the injection site.The pH at which the amount of ionised and nonionised drug is equal is known as the pka or diffusion constant , (the pKa of lignocaine is 7.8 but at a pH of 7.4, more than half of the drug exist as charged cation)  The onset of action of the drug is determined by the dissociation constant and pH of the medium. Anaesthetic with a pKa value near the physiological pH has a greater proportion of drug in the non-ionised form. The non ionised form  diffuses more readily across the nerve sheaths and membrane to its site of action. Therefore, local anaesthetics with pKa values close to physiological pH tend to have a more rapid onset of action as the non ionised content of the drug is more.  Factors that promote local extracellular acidosis (eg: infection) increase drug ionisation and therefore reduce local anaesthetic diffusion and penetration of the nerve membrane. Addition of sodium bicarbonate (1 ml 8.4%  sodium bicarbonate per 19 ml 1 % lignocaine)to local anaesthetics increases the pH of the solution, which increases the ratio of non-ionised to ionised form,resulting in a more rapid onset of action. The potency of local anaesthetics is affected by its lipid solubility  A highly lipid-soluble drug readily penetrates cell membranes and thus have higher potency compared to drugs having lower lipid  solubility

The degree of protein binding( alpha 1 acid glyco protein) and vascularity also affects the local anaesthetic’s
duration of action. Those with high plasma protein binding have longer durations of action. Addition
of a vasoconstrictor like epinephrine to lipid  soluble local anaesthetics decreases vascularity at the injection site, which prolongs the duration of action (via reduced absorption of the drug into the systemic circulation).

Mechanism of action:

LAs are membrane-stabilising drugs that reversibly decrease the rate of depolarisation and repolarisation of excitable membranes.Local anaesthetics block sensory and motor function by impeding the permeability of
neuronal cell membranes to sodium. This action prevents the rapid influx of sodium during the depolarisation phase of the action potential and its onward transmission.LAs selectively bind to inactivated closed sodium channels and stabilise them in order to prevent channel opening due to nerve stimulation and subsequent propagation of action potential.The primary electrophysiological effect of these compounds is to cause a local decrease in the rate and degree of depolarisation of the nerve membrane such that the threshold potential for transmission is not reached and the electrical impulse is not propagated down the nerve.[2]

Metabolism: The ester type local anaesthetics are hydrolysed by esterases in tissues and blood, while the amide types are metabolised primarily in the liver by cytochrome P450 enzymes and then excreted through kidney. Dosage adjustments may be made in hepatic and renal failure.[2]

Calculation of percentage  and dosage:

Concentration. Drug concentration is expressed as a percentage, i.e. grams per 100ml (e.g. 1%=1 g/100 ml (1 000 mg/100 ml) or 10 mg/ml). (Bupivacaine 0.25%=2.5 mg/
ml; lignocaine 1%=10 mg/ml.)
Dilution. When adrenaline is combined in an anaesthetic solution the result is expressed as a dilution (e.g. 1:100 000):
• 1:1 000 means 1 mg/1 ml (0.1%)
• 1:10 000 means 1 mg/10 ml (0.01%)
• 1:2 000 means 1 mg/2 ml (0.05%)
• 1:20 000 means 1 mg/20 ml (0.005%)
• 0.1 ml of 1:1 000 adrenaline added to 10ml of anaesthetic solution = 1:100 000 dilution or 0.01 mg/ml
• 50 ml of lignocaine 1% with adrenaline 1:100 000 contains lignocaine 500 mg and adrenaline 0.5 mg.
Adrenaline is the most commonly used vasoconstrictor, it is added to local anaesthetic solutions in concentrations ranging from 1 in 80,000 to 1 in 300,000, although most are usually prepared to contain a 1 in 200,000 (5 microgram /ml) concentration of adrenaline.[3]

Practical Point 

Adrenaline 1:1000 contains 1 gram of adrenaline per 1000mls solution i.e. 1mg/ml. To prepare a 1 in 200,000 solution the 1:1000 must be diluted 200 times. This is achieved by taking 0.1ml (= 0.1mg) and adding 19.9 mls of local anaesthetic solution.

Etiology of toxic reactions to Local Anaesthetics:[1]

• Systemic: CNS  and CVS toxicity, termed as local anaesthetic systemic toxicity or LAST

• Local toxicity: Neuronal damage or skeletal muscle damage

• Others:   Methemoglobinemia (prilocaine) Hydrolysis of prilocaine initially leads to the formation of o-toluidine products that bind to haemoglobin and oxidises Hb to ferric form and cause methaemoglobinaemia.

•  Allergy: Allergic reactions are rare even though IgE mediated reactions can occur and may be seen with ester linked LAs.

• Addiction:  Cocaine  may lead to drug dependance.

• Reaction to vasoconstrictors: Tachycardia, hypertension, headache,apprehension, which usually need no treatment.

• Vasovagal reaction: Rapid onset of bradycardia, hypotension, pallor,faintness.Usually seen when patient assumes sitting position.

• Anaphylaxis: Hypotension, bronchospasm, urticaria, oedema, needs treatment as per anaphylaxis algorithm

• Transient nerve damage like persisting paraesthesia, prolonged anaesthesia etc will resolve spontaneously  and permanent nerve damage is rare. 

Local anaesthetic systemic toxicity (LAST)

Toxicity may occur due to[2]

1. Accidental intravascular or intrathecal injection
2. Relative overdosage of drug used
3. Rapid systemic absorption  from the injected site

CNS Toxicity: Symptoms and signs of CNS  toxicity are  manifested as initial excitation  followed by depression. The pre excitation phase is characterised by tinnitus, light headedness ,confusion and circum oral numbness and paraesthesia. This progresses on to the excitation phase where the signs are shivering, tremor muscular twitchings  and convulsions .The final stage of depression is fatal as patients may loose consciousness and may go in for respiratory arrest. Blockade of inhibitory pathways  and inhibition of release of glutamate in cerebral cortex produce initial excitation.Blockade of inhibitory pathways allows facilitatory neurons to function in an unopposed fashion, which results in an increase in excitatory activity leading to convulsions. A further increase in the dose of local anesthetic leads to inhibition of activity of both the inhibitory and facilitatory circuits, which results in a generalized state of CNS depression.Respiratory or metabolic acidosis increases CNS toxicity by increased  cerebral blood flow and resulting in rapid delivery of anaesthetic agents to brain.Acidosis also decreases intracellular pH resulting in iron trapping, decreases the plasma protein binding making available more free form of the base. Seizures produce hypoventilation and a combined respiratory and metabolic acidosis, which further exacerbates the CNS toxicity. Hence immediate support of airway with proper ventilation and meticulous control of seizures advised,in LA toxicity

CVS Toxicity:  Direct cardiovascular effects  and direct peripheral vascular effects are observed .The direct CVS effects include bradycardia due to action on sodium channels which reduces action potential duration and effective refractory period.They increase PR interval and QRS complex duration resulting in prolongation of conduction time.They also exert dose-dependant negative inotropic action on cardiac muscle.Local anesthetics may depress myocardial contractility by affecting calcium influx and triggered release from the sarcoplasmic reticulum,[2] The direct peripheral vascular effects include a biphasic response on vascular smooth muscles characterised by initial vasoconstriction followed by vasodilatation.Thus there will be a reduction in blood pressure. The toxic effects are more pronounced with bupivacaine and remain sustained.Ventricular arrhythmias  including fibrllation are more common with bupivacaine  and cardiac resuscitation is more difficult after bupivacaine-induced cardiovascular collapse, and acidosis and hypoxia markedly potentiate the cardiotoxicity of bupivacaine.(4)

Treatment of  LAST:

In 2007, the Association of Anaesthetists of Great Britain and Ireland published guidelines for the
management of severe local anaesthetic toxicity.[5] In 2008, the American Society of Critical Care Anesthesiologists and the American Society of Anesthesiologists Committee on Critical CareMedicine,[6] as well as the Resuscitation Council of the United Kingdom[7] also published protocols for the treatment of LAST. In 2010, the American Society of  Regional Anesthesia and Pain Medicine published its practice advisory on LAST.[8] These guidelines emphasise the importance of airway management and early cardiopulmonary resuscitation, They also strongly  advise use of lipid emulsions along with resuscitative measures  and have incorporated the use of lipid emulsion therapy in their guidelines, in the management of LAST. The AAGBI  algorithm is shown below.

What is intra lipid?  How it helps?

Intralipid is a brand name for the first safe fat emulsion for human use, approved in 1962 in Europe and invented by Professor Arvid Wretlind, Sweden.   It is used as a component of parenteral nutrition for patients who are unable to get nutrition via an oral diet. It is an emulsion of soy bean oil, egg phospholipids and glycerin. It is available in a 10%, 20% and 30% concentration. The 30% concentration is not approved for direct intravenous infusion, but should be mixed with amino acids and dextrose as part of a total nutrient admixture.Intralipid provides essential fatty acids, Linolenic acid (LA), an omega-6 fatty acid,alpha-linolenic acid(ALA), an omega-3 fatty acid. Some preparations of the anaesthetic drugs propofol and etomidate (the vehicle for etomidate is propylene glycol) are supplied using Intralipid as a vehicle.[9] Intralipid is widely and freely available in all hospital intensive care units as this is one of the major constituent of parenteral nutrition

In 1998 Weinberg et al[10] first reported that lipid emulsion infused during resuscitation increased the
median lethal dose (LD50) of bupivacaine in rats by 50%. Followed by  in 2006 Rosenblatt et al[11] and
Litz et al[12] reported successful clinical use of lipid emulsion to reverse local anaesthetic induced cardiac
arrest.Many clinical reports released after this supported the use of lipid emulsion in the management of LAST[13,14,15] caused due to bupivacaine, levobupivacaine, and  ropivacaine.

The exact mechanism of action of lipid emulsion therapy is not known. It may serve as a“lipid sink”, providing a large lipid phase in the plasma, enabling capture of the local anaesthetic molecules and making them unavailable to tissues.Alternatively they prevent impaired fatty acid delivery caused by local anaesthetics in the mitochrondria, and enhance energy production. The commonly used lipid emulsion preparation is Intralipid 20%, and the efficacy of other preparations is not studied in detail . Propofol is not asuitable substitute for Intralipid. It is formulated in a 10% lipid emulsion as the amount of lipid emulsion is less compared to the concentration of propofol and higher doses of propofol have direct cardiovascular depressant effects. The recommended Intralipid regimen as given by AAGBI, entails an initial intravenous bolus injection of a 20% emulsion at 1.5 mL/kg over 1 minute, followed by an infusion of 15mL/kg/h. Cardiopulmonary resuscitation should be continued. If cardiovascular stability is not restored after 5minutes or if haemodynamics deteriorate, a maximum of two repeated boluses (1.5 mL/kg) may be given at 5-minute intervals. The intravenous infusion rate should also be doubled to 30 mL/kg/h. A maximum of three boluses can be given, and a cumulative dose of 12 mL/kg should not be exceeded.
 
It is seen that increasing the dose beyond 8 mL/kg is unlikely to be useful and in practice, resuscitation of an adult weighing 70 kg is  as follows:

1. Use a 500-mL bag of fat emulsion (Intralipid 20%) and a 50-mL syringe.
2. Draw up 50 mL and give it stat intravenously, and then draw up and give another 20 mL.
3. Do exactly the same thing up to twice more as the epinephrine is given—if necessary or appropriate.
4. Then, attach the fat emulsion bag to a giving set and administer it intravenously over the next 15 minutes.

Contra-indications to lipid emulsion therapy include lipid metabolism disorders and egg allergy, and caution is required for patients with anaemia, severe liver disease, coagulopathy, and pulmonary disease.  Potential complications include allergic reaction, fluid overload, impaired liver function, hypercoagulability and pancreatitis.
                                                                                                                                                         
Here is the great and eminent personality whom i admire and salute,  Dr. Weinberg,a pioneer behind this experimentation and who first postulated that lipid emulsion has a role in the treatment of LA toxicity. Following his second report in 2003 stating that "Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity"., published in Regional Anesthesia and Pain Medicine 2003; 28: 198-202, many case reports have been published in support of the efficacy of lipid emulsions for reversing local anaesthetic toxicity.[13,14,15] He himself has designed a web site and shared his experience knowledge and invited people from all over the world for contributions in this regard .The site deals with local anaesthetic toxicity, literature, case reports,experiments, and treatment regimen.He has designed the lipid rescue kits and is running a laboratory for further research on this issue  watch this site:    www.lipidrescue.org
This figure shows a Home made lipid rescue kit .This kit designed by Mike Alway, RPh, from BonSecours Hospital.  "The container for the kit is a blue storage bin that has a clear hinged lid.  It contains the 20% Lipid bag (500 ml), IV tubing, 60cc Syringes (2), and needles. The protocol is attached to the Lipid bag inside the kit and  also pasted it on the outside.

           





So make your own rescue kits today and keep them in OR within your reach.

Reference:

1.KC Lui;YF Chow, Safe use of local anaesthetics: prevention and management of systemic toxicity; Hong Kong Med J 2010;16:470-5
2. Miller's Anaesthesia,7th edition, R D Miller et al , Churchil Livingston
3.René du Plessis, MB ChB,Specialist Anaesthetist,Bloemfonte, Local anaesthetics: Characteris tics, uses
and toxicities;CME September 2009 Vol.27 No.9
4.Englesson S: The influence of acid-base changes on central nervous system toxicity of local anaesthetic agents. An experimental study in cats.  Acta Anaesthesiol Scand  1974; 18:79-87.
5.Guidelines for the management of severe local anaesthetic toxicity. The Association of Anaesthetists of Great Britain &Ireland; 2007.
6.Gabrielli A, O’Connor MF, Maccioli GA. Anesthesia Advanced Circulatory Life Support. The American Societyof Critical Care Anesthesiologists & The American Society of Anesthesiologists, Committee on Critical care Medicine;2008.
7.Cardiac arrest or cardiovascular collapse caused by local anesthetic. Resuscitation Council (UK); 2008.
8.Neal JM, Bernards CM, Butterworth JF 4th, et al. ASRA practice advisory on local anesthetic systemic toxicity. RegAnesth Pain Med 2010;35:152-61.
9.Wikipedia, en.wikipedia.org/wiki/Intralipid.
10.Weinberg GL, VadeBoncouer T, Ramaraju GA, Garcia-Amaro MF, Cwik MJ. Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaineinduced
asystole in rats. Anesthesiology 1998;88:1071-5.
11. Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, EisenkraftRosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB. Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest.Anesthesiology 2006;105:217-8.
12.Litz RJ, Popp M, Stehr SN, Koch T. Successful resuscitation of a patient with ropivacaine-induced asystole after axillary plexus block using lipid infusion. Anaesthesia 2006;61:800-1.
13.Julio A. Warren, MD,R. Brian Thoma, MD, Alexandru Georgescu, MD,Saurin J. Shah, MD
Intravenous Lipid Infusion in the Successful Resuscitation of Local Anesthetic-Induced Cardiovascular
Collapse After Supraclavicular Brachial Plexus Block (Anesth Analg 2008;106:1578 –80)
14.Meg A. Rosenblatt, M.D., Mark Abel, M.D., Gregory W. Fischer, M.D.,Chad J. Itzkovich, M.D.,James B. Eisenkraft, M.D; Successful Use of a 20% Lipid Emulsion to Resuscitate a Patient after a Presumed Bupivacaine-related Cardiac Arrest
15. R. J. Litz,M. Popp,S. N. Stehr,  Anaesthesia, Volume 61, Issue 8, pages 800–801, August2006, Successful resuscitation of a patient with ropivacaine-induced asystole after axillary plexus block using lipid infusion.