Specialist Neurologist, Aster specialty clinic, International city, Dubai, UAE

Dr Vishal Pawar

Dizziness is a common complaint in medical outpatients, with vestibular disorders being the most common cause of dizziness.1-3 However, there is little data available describing the incidence of vestibular disorders in the Dubai population.4 This study therefore aims to report the etiological spectrum of vertigo and dizziness from a vertigo speciality clinic in Dubai. 

The study was conducted at the Vertigo clinic, Aster Specialty Medical Centre, International city, Dubai, which is equipped with Video-Oculography (VOG) goggles. All patients suffering from dizziness who visited the Vertigo clinic during the study period (27th Jan-25th Dec 2019) were included in the study (n=601). Detailed history taking and neurotological examination were performed in every patient. Video-oculography (VOG), Neuroimaging studies and other investigations were also conducted where appropriate. 

During the 11-month study period, 601 patients (359 males and 242 females) were evaluated. The mean age was 38 years (Range 14-83 years).



Overall, central causes were responsible for 47% cases; peripheral causes were seen in 31% cases, functional and psychiatric causes in 12% of patients and other causes in 9% of cases. Vestibular migraine was the most common central cause, Benign paroxysmal positional vertigo (BPPV) was the most common peripheral cause, and persistent-postural-perceptual dizziness (PPPD) was the most common cause of dizziness due to functional aetiology. 



Vestibular migraine is the leading cause of spontaneous episodic vertigo. 

The International classification of headache disorders (ICHD-3) criteria was used to diagnose vestibular migraine.

Due to the stringent nature of the diagnostic criteria, only 25% patients with vestibular migraine were diagnosed to have ‘definite’ vestibular migraine, and 75% were diagnosed to have ‘probable’ vestibular migraine

Patients with ‘definite vestibular migraine’ had vertigo as a presenting complaint which affected their quality of life. The duration of the dizziness was more than 5 minutes per episode. 

Patients with ‘probable vestibular migraine’ did not have vertigo as a presenting complaint, and many reported that it did not affect their quality of life. A large proportion of patients had a duration of dizziness of less than 5 minutes. Some patients had had fewer than 5 attacks of vestibular symptoms. Of those who had more than 5 attacks, fewer than 50% of the attacks were associated with 2 or more of the four migrainous features mentioned in the diagnostic criteria2. All of these patients were categorized as ‘probable vestibular migraine

A statistical analysis showed the following findings.

258 patients were diagnosed with vestibular migraine. 

69 patients presented with migrainous positional vertigo mimicking BPPV. 

15 patients presented with Meniere’s syndrome. 

51 patients presented with pseudo- acute unilateral vestibulopathy, and 5 patients presented with bilateral vestibulopathy 

The mean age of onset of vestibular migraine was 38 years.

Vestibular migraine can affect children as young as 14 years, and can present as late as 83 years.

It is slightly more common in females (53.48% of cases) than in males. 

Video-oculography showed dizziness and discomfort on optokinetic stimulation in 90% of patients.

13.5% (35/258) patients with vestibular migraine had co-morbid/triggered persistent-postural-perceptual dizziness 

22% of patients had a history of motion sickness in childhood (39/258). 

Overall, BPPV was the second most common cause of vertigo. However, it remains the most common cause of positional vertigo if ‘probable vestibular migraine’ patients are discounted. 

108 patients had typical symptoms suggestive of BPPV (Fig 3).

11 patients did not undergo positional testing. Of those who underwent positional testing (97 patients), 49 patients had nystagmus which was characteristic of one of the canal types (objective BPPV). 

30 patients had symptoms without any characteristic nystagmus during the positional testing (subjective BPPV). 10 patients with Subjective BPPV (sBPPV) had sitting-up vertigo (or Type 2 BPPV), and 20 patients were classified as having sBPPV forms other than type 2 BPPV. 
7 patients did not have symptoms or nystagmus during the positional testing. They were classified as ‘probable BPPV spontaneously resolved’ as per the Barany society criteria. 


The most common type of objective BPPV was posterior canal (65%), followed by the lateral canal (24%). Anterior canal BPPV was seen in 10% of patients. 

30 out of 32 patients with posterior canal BPPV had a typical form, and two patients had an apogeotrophic form (Fig 4). 10 out of 12 patients with lateral canal BPPV had the geotrophic form, and two patients had the apogeotropic form. 

3) Persistent postural perceptual dizziness: 

86 patients were diagnosed to have ‘persistent postural perceptual dizziness’ (P3D). P3D presents with chronic vestibular syndrome. 

Symptoms are usually triggered in specific situations such as crowded places (malls, supermarkets), which can be classified as agoraphobia. Symptoms can also be triggered in open places during active or passive head motion (especially while driving). The symptoms usually present with the patient in an upright posture, and are relieved in the supine position. 

In 34 patients, the precipitating disorder for the P3D could not be established. Fifty-two patients had P3D secondary to another vestibular, neurologic or medical disorder. 

The most common precipitating disorder for P3D was vestibular migraine. Other vestibular disorders identified included BPPV, Meniere’s disease, Acute unilateral vestibulopathy and vestibular paroxysmia. However, it was observed that P3D could also be triggered by non-vestibular disorders including epilepsy and depression. 

The most common oculographic finding in patients with P3D was ‘dizziness during a hyperventilation test without any characteristic nystagmus.

30 patients were diagnosed with Meniere’s disease. This can trigger persistent-postural-phobic dizziness. It closely mimics vestibular migraine and differentiation from vestibular migraine can sometimes be challenging. 

18 cases were diagnosed with acute unilateral vestibulopathy due to peripheral aetiology (p-AUV). Patients with p-AUV presented with acute vestibular syndrome. Following the HINTS examination protocol is essential in these cases to exclude central causes. All patients had a positive head impulse test, unidirectional nystagmus without fixation, absence of skew deviation and absence of acute hearing loss. 

The nystagmus of p-AUV is not seen under light during a routine clinical examination, or is of mild intensity when gazing contralateral to the side of a vestibulopathy. 

Examination of the eyes in the dark (especially with videonystagmography (VNG) goggles and visor), or with Frenzel lenses, is the key to the diagnosis of a unidirectional nystagmus. 

Three cases were diagnosed to have Ramsay Hunt syndrome presented with an acute unilateral vestibulopathy. They had ipsilateral facial weakness and herpetic lesions in-ear (Fig 5). 

16 cases of dizziness were secondary to trauma. 8 were diagnosed with BPPV and 5 had a labyrinthine concussion. Patients with labyrinthine concussion presented with ‘acute vestibular syndrome’. Two patients had both BPPV and labyrinthine concussion. 

Dizziness of psychiatric origin was seen in 14 out of 601 patients (2.3%). The most common cause was anxiety disorder. 

13 cases were diagnosed with vestibular paroxysmia. They commonly presented with a spontaneous episodic syndrome of chronic onset. 

All patients had stereotypical symptoms lasting less than one minute per episode. 

Two cases had co-existent trigeminal neuralgia.

Two cases had positionally triggered attacks of vertigo. 
3 out of 6 patients who underwent VNG showed hyperventilation nystagmus.


MRI brain showed an arterial loop in 9 patients (Fig 6), a venous loop in 1 patient and 3 cases of secondary paroxysmia (multiple sclerosis, vertebral dolichoectasia and an arachnoid cyst in the cerebello-pontine angle respectively)

All patients with vestibular paroxysmia showed a complete response to carbamazepine and/or gabapentin.

9 cases had vestibular symptoms originating from a vascular cause. 4 patients had an infarction in the vertebro-basilar distribution. Three cases had transient ischaemic attacks; one patient had a cerebellar bleed, and one case had vertebral artery compression syndrome. 

6 patients were diagnosed to have posterior fossa tumours. Three had a cerebellopontine angle tumour; the three remaining cases were respectively diagnosed to have an arachnoid cyst, a colloid cyst of the third ventricle and retro-cerebellar meningioma.

6 patients had drug-induced dizziness. The incriminating drugs were as follows.

Combination of candesartan, dutasteride and alfuzosin

20 patients had syncopal (Type-2) dizziness. The causes were as follows: 

Postural orthostatic tachycardia syndrome- 3

16 patients were diagnosed to have other disorders as follows.

The cause could not be established in 21 cases, despite a detailed history and relevant investigations. 

Vestibular migraine is one of the most common causes of spontaneous dizziness. BPPV is the most common cause of positional vertigo. This study is probably one of the most extensive studies of vertigo patients in a Dubai population from a neurology clinic. The etiological spectrum of vertigo seen in this study is similar to spectra reported from other countries

Sen K, Sarkar A, Raghavan A. The vertigo spectrum: A retrospective analysis in 149 walk-in patients at a specialised neurotology clinic. Astrocyte 2016;3:12-4.

Das S, Chakraborty S, Shekar S. Dizziness in a Tertiary Care Centre in Sikkim: Our Experience and Limitations. Indian J Otolaryngol Head Neck Surg. 2017;69(4):443-448.

Edlow JA, Newman-Toker D. Using the Physical Examination to Diagnose Patients with Acute Dizziness and Vertigo. J Emerg Med. 2016;50(4):617-628.

Desai TD, Amini SS, Asad F, Kutty H. Prevalence of vestibular migraine in Dubai. Hamdan Med J 2019;12:19-22.

Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia 2018;38(1):1-211

The Etiological Spectrum of Dizziness Observed at a Vertigo Clinic: A Study of a Dubai Outpatient Population

#111827

Chief Medical & Quality Officer at Aster DM Healthcare

Dr A Malathi

Lessons learned from Aster DM Healthcare Hospitals in India & GCC.

Aster DM Healthcare has been at the epicentre of managing COVID-19 pandemic in India and Gulf Cooperation Council countries ever since the pandemic hit in mid-March. This paper is a fascinating organisational case study and report about how Aster DM healthcare navigated the challenge of COVID - 19 Pandemic.

The 2020 COVID-19 Pandemic has made society and the global economy volatile, uncertain, and ambiguous, even though high levels of preparedness have been developed for the situation. Late 2019, and early 2020, when the Coronavirus outbreak was limited to China, there was little expectation that it would grow to such pandemic proportions. No aspect of life, including business ventures, has been left untouched by this scourge. While the world stands still due to the COVID-19 pandemic, the impact that this disease has had on healthcare systems in various countries has been profound. Healthcare organizations, along with government functionaries from across the country, have delved into innovative ways to battle the disease, and have devised policies and protocols to ensure continuity of care and therapy for both COVID and non-COVID patients, within the ambit of safety for both patient and healthcare workers.

This paper provides a case study of how ASTER DM Healthcare handled the COVID-19 situation, to keep afloat both clinical and operational functions while ensuring the safety of healthcare workers. This was achieved by adopting new protocols based on updated scientific information and guidance from thought leaders across the Aster Group, which enabled the leadership team and staff at Aster to plan and respond swiftly to the daily dynamic uncertain environment created by the COVID-19 onslaught.

An outbreak of the respiratory disease was reported from Wuhan, a city of 11 million people in China, on 31st December 2019. The causative agent was discovered in January 2020 to be a novel enveloped ß-coronavirus of the same sub genus as SARS-CoV,1 and has been named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also called Coronavirus disease 2019 (COVID-19).2 Novel Corona Virus (SARS CoV2 / COVID-19) is a highly contagious infection and has been declared as a pandemic by the World Health Organization. It is important to be vigilant about the spread of the disease and be able to provide the rapid implementation of outbreak control and management measures. The lack of a proven treatment and vaccine as well as the high vulnerability of hospital staff makes it imperative to have guidelines as to how we can protect healthcare workers.

Hospitals are complex and vulnerable institutions, dependent on crucial external support and supply lines. Under normal working conditions, many of our hospitals frequently operate at near-surge capacity. Consequently, even a modest rise in admission volume can overwhelm a hospital beyond its functional reserve. Well-established partnerships with local authorities, service providers (e.g. of water, power, and means of communication), supply vendors, transportation companies, and other organizations are required to ensure the continuity of essential services.

During the current outbreak of COVID-19, well-prepared health facilities are at the center of an effective response. The rapidly evolving outbreak requires all hospitals to be able to adapt to a swift increase in demands while continuing to ensure safe environments for health workers. All hospitals need to take precautions against potential interruptions of critical support services and shortages of equipment and supplies. This document aims to provide a Risk Assessment and mitigation strategy based on lessons learned from Aster DM Healthcare Hospitals in India & GCC.

Also, a high rate of staff absenteeism can be expected. A shortage of critical equipment and supplies could limit access to needed care and have a direct impact on healthcare delivery. Panic could potentially jeopardize established working routines. Even for a well-prepared hospital, coping with the health consequences of a COVID-19 would be a complex challenge. Despite the difficult demands and obstacles foreseen, the proactive and systematic implementation of key generic and specific actions facilitated effective hospital-based management during a rapidly evolving pandemic.

Well-prepared health facilities is the key to saving the lives of COVID-19 patients. Preparations have been well done for global outbreaks and disasters in our system with our knowledge & experience from Kerala floods and the Nipah virus outbreak. On 30 January 2020, a public health emergency of international concern was declared by the World Health Organization (WHO). We activated our incident command centers across the group and carried out a rapid risk assessment. The overall objective was to strengthen the preventive action to reduce COVID-19 risk and enable Aster to take a timely and useful response. Priority measures were identified based on significant references like WHO, CDC, and national guidelines. An executive council was established to cascade our business units with effective strategic plans.

As the COVID-19 situation is rapidly evolving, Aster focused on developing clinical guidelines for healthcare workers in concurrence with international organizations like WHO, CDC etc. The clinical excellence was achieved by implementing updated guidelines which were constantly shared with healthcare providers in order to achieve the best patient outcomes. Our COVID dashboards helped us to monitor our outcomes and at the same time, providing insight into improvement strategies in patient care. 

MANAGEMENT OF COVID CASES AT THE FIRST POINT OF CONTACT

On 30th January 2020, the WHO declared COVID-19 a public health emergency which soon evolved into a pandemic. From the early days of this disaster, Aster DM has been working tirelessly with the local authorities to prepare its response to the disease. 

One of the major elements of the response was the set-up of more than 4 facilities with a total capacity of 800 plus beds which helped control the spread of the virus. Meanwhile the hospitals stopped their elective activities and focused almost entirely on the management of the suspected and confirmed cases. 

The COVID response team in hospitals decided to dedicate the emergency departments to the management of suspected cases and the wards and ICUs were dedicated to the management of confirmed cases. As a consequence, the more severe cases were taken directly to the wards or the ICUs and the number of severe cases seen in the ERs remained very low. The vast majority of the patients who attended the ER’s were suspected cases that needed a confirmation or confirmed cases who required screening before isolation. Most of them were clinically well. Despite this organisation the ERs received a few severe cases and the level of response was exemplary. A few cases have been highlighted to showcase the quality of the emergency response:

A 62-year-old male patient was admitted in one of the isolation hotels, having been referred directly by DHA (Dubai Health Authority). The patient did not have any identified risk factors other than being over the age of 60. He was not obese and had no co-morbidities identified at the time. He tested positive for COVID-19 after a period of persistent cough and fever. 12 hours after admission he was found to be hypoxic on room air and was promptly transferred to the ER. On arrival, he was found to be conscious and responsive, patent airway, breathing at a rate of 24 per minute, saturation on room air was 70% and only reached 85% with 10 liters of supplemental oxygen delivered via a non-rebreathing mask. His cardiovascular parameters were within normal limits and stable with a pulse of 71 bpm and a BP of 128/62. His GCS was 15 with no neurological deficit. An arterial blood gas showed a respiratory failure of type 1. A chest X-Ray showed a picture evocative of atypical pneumonia compatible with corona virus. 

The patient was immediately referred to ICU for further investigations and management. The NIV was not started in the ER due to the speed at which the patient could be moved to a more appropriate environment given the risk of contamination of staff that is associated with the procedure. 

The patient was successfully managed conservatively in ICU without intubation before being discharged home.  This case highlights the excellent level of teamwork that was displayed throughout the COVID crisis. The coordination and communication between the different teams (hotel staff, ambulance team, ER and ICU staff) was excellent, and ensured permanent safety for the patient and the members of staff in spite of the challenging circumstances. 

A 67-year-old male patient was brought to the ER by national ambulance in cardiac arrest. The patient was a confirmed case of COVID who was in self isolation at home and was known to suffer from diabetes, hypertension and cardiac failure. The staff members were pre alerted and had enough time to get prepared and were wearing full PPE when the patient arrived. The patient presented a trismus which was probably an early sign of rigor mortis. He was managed following the ACLS protocol for 40 minutes with continuous CPR and adrenaline on alternate cycles, before he was declared dead in view of the lack of response to the resuscitative attempt. 

Despite the poor outcome, this case highlighted the level of preparedness of the all the emergency staff members. The case was managed calmly and professionally in full respect of staff safety measures, by the means of PPE. There was no precipitation and every step of the ACLS protocol was followed without failure. 

These two examples demonstrate that, after weeks of training and with the help of the infection control team, internal medicine and intensive care, the ERs have been able to safely manage critical cases in the most professional manner. 

Despite the constantly growing feeling of anxiety, and despite some serious technical challenges posed by the nature of the infectious agent, the team has shown a real level of maturity in this unique crisis management. 

MANAGEMENT OF CRITICAL CARE  PATIENTS IN PANDEMIC

Medcare Hospital partnered with DHA in March 2020 and we started preparing the critical care unit to accommodate and manage such cases by increasing the number of rooms with negative pressure. 

As we strongly believe that prevention is most effective at the start, we immediately took measures to prevent and limit transmissions between the hospital staff, and protect the healthcare workers in accordance to the international and national COVID-19 precautions guidelines. This included the availability of PPE and proper use and disposal of the protective equipment. Continuous education and close communication with the infection control team have been at the core of the initial phases of our plan of facing the pandemic.

We formulated and set up guidelines and protocols derived from the recommendations of surviving sepsis guideline 2020 - special edition for COVID, World Health Organization.

We soon started receiving cases of different nationalities. We have noticed that we have a considerably higher number of male patients compared with female patients, most of them between 30 and 60 years old. But these observations have to be taken in the context of Dubai’s special demographic (higher number of male residents, most of them young or middle aged.)

Most of the patients presented with complaints of fever and some degree of difficulty in breathing. We observed that a significant number of patients presented with low levels of PaO2 and SpO2 without clinical signs, symptoms, or visible distress - silent hypoxia. 

Most of our patients showed worsening of the symptoms in the second week of disease, many times after a few days of improvement, which can give a false sense that patient is starting the recovery phase. This second phase of the disease is when most of the critical care patients end up on ventilator. A small percentage of those in respiratory failure are improving on NIV, thus we chose to initially give a trial for most of our patients with noninvasive support if tolerated before going for intubation. 

Once the patient had an ET tube in place we faced one of our biggest challenges, which was sudden ET tube blocks with large clot and necrotic tissues. Despite daily proper suctioning (closed and opened) on the ET tube, the high majority of patients required ET tube to be frequently changed due to acute blockage with clots (in some cases more than once per day). In our ICU all ventilated patients have been started on heparin nebulization and this therapy seems to offer some decrease in the need for change of ET tubes.

Although all specific ARDS ventilation recommendations have been used, we have soon realized that this is not the “classic” ARDS picture with stiff lung that we are facing, as there was not a requirement for high plateau pressures to obtain satisfactory tidal volumes (6-8 ml/kg), but despite the high volumes, patients remained severely hypoxic even at very high PEEP and hypercapnic, (situation associated more with pulmonary embolism). Prone position offered some relief in patients with refractory hypoxia (it has to alternate with supine every 8 to 10 hours). 

 For the patient that required prolonged ventilation we opted for percutaneous tracheostomy which made it easier to deal with recurrent tube blockage, and difficult weaning mainly due to hypercapnia. 

We have noticed that intensive chest physiotherapy is worsening the patient’s ventilation, thus we opted for mild or no chest physiotherapy in the initial phases of the disease in critical patients and to return to usual physiotherapy in the recovery phases. 

Though this masquerading virus was affecting the oxygenation and ventilation of the patient, it gave us more challenging complications such as thrombotic events like ACS ischemic stroke, acute tubular necrosis and pulmonary embolism. A considerable percentage of our patients were developing myocarditis and acute coronary syndrome pictures. Thus all our patients have been started on enoxaparin therapeutic dose and Aspirin. After this protocol had been put in place it was noticed that there was a decrease in the thrombotic complications. In one case in which Thromboembolisation was required for acute MI, a significant improvement in ventilation was noticed, but unfortunately only for 24 hours after the therapy. 

We have also noticed that all patients admitted in ICU have very high levels of D dimers, Ferritin, CRP. The D- dimers levels were found to be between 3000 and more than 30000, and it looks like there is a direct correlation between these lab levels and the course of the disease. Trombocytopenia have been also noticed, but only mild to moderate decrease of platelets levels. In one case in which thrombolization had been required for acute MI, an improvement in ventilation was also noted. Among dyselectrolytemias Phosphate levels have been found to be low in almost all critical COVID-19 patients.

It has been noticed that patients recovering from severe form of the disease are left with Chronic/ permanent lung damage. Most of the patients that have recovered from moderate/severe ARDS form of COVID 19, have been discharged with radiological images suggestive of lung fibrotic changes from mild to extensive. In one particular case, the changes were accompanied by the presence of emphysema and large bullae which complicated with spontaneous pneumothorax. There is a need to follow these patients in the future and assess their outcomes on a long term basis.

Managing the corona virus infected patient 

In accordance to the surviving sepsis guidelines, we started general management like any other septic patient . Although we were initially following the fluid restriction recommendations, we have soon decided to use the initial fluid resuscitation as per patient needs in hemodynamically unstable patients, using minimally invasive cardiac monitoring and assessing patient’s fluid responsiveness, followed by deresuscitaton when patient is out of the shock phase.

Along with the specific support of functions, we included in our protocols virus specific management which included the use of antivirals as recommended by the national and international protocol. The anti-viral agents that were used included (lopnavir/ritonavir, favipiravir). Immunomodulatory drugs such as tocilizumab, have been also used in critical patients which showed some benefit. 

Managing the thrombotic complications of the corona virus was a challenge we faced every day. We used subcutaneous anti-coagulants (LMWH in the therapeutic dose). We used anti-platelets including (Aspirin and Plavix). We used NOACs (rivaroxaban) in stable COVID-19 patients with mild pneumonitis. 

Facing the ET blocks, we used heparin nebulizations with which showed some decrease in the frequency of changing ET tubes.
Early tracheostomy showed a better outcome in patients on long ventilator time due to refractory hypercapnia. 
We used prone position for the patients with severe ARDS with refractory hypoxia. Some improvement in the oxygenation have been noticed



There are still many unknown aspects of the infection with SARS-Cov2 virus. These major knowledge gaps make dealing with critical patients with COVID-19 a special and unprecedented challenge. There is a need to continuously adapt the current guidelines, as new managements with a strong evidence base and new therapeutic options are emerging.

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*Disclaimer: The situation regarding COVID-19 is rapidly evolving and changes daily. Although timely policies should be implemented to facilitate objective decision-making, such directives will inevitably need to adapt to this fluid environment. This document content stands as on date. Visit the article page at www.theamj.org to access the full version of the Whitepaper along with the details of mitigations strategies implemented by the individual Aster hospitals in India and GCC.

COVID-19: Risk Assessment &Mitigation Strategy

Dr Binesh Balachandran

Being a developing country and with its own limited resources, sepsis-related mortality and morbidity are perhaps the most prevalent in India. We often ascertain a number of “sepsis variant” diagnoses in our clinical practice. Definite sepsis, probable sepsis, early onset neonatal sepsis, late onset neonatal sepsis, suspect sepsis and even culture negative sepsis!

Neonatal sepsis remains a major problem in NICUs, as possibly the most commonly diagnosed/suspected and treated illness in NICUs around the world. Being a developing country and with its own limited resources, sepsis-related mortality and morbidity are perhaps the most prevalent in India. We often use a number of “sepsis variant” diagnoses in clinical practice- definite sepsis, probable sepsis, early onset neonatal sepsis, late onset neonatal sepsis, suspect sepsis and even culture negative sepsis!

One drawback of being “over familiar” with sepsis is that many of us tend to attribute each and every symptom and illness to sepsis in some way. We often resort to our own clinical acumen or gut instinct rather than using evidence-based methods to reach such a diagnosis. Many of us are hypocritical in that we take supporting lab investigations at face value only when the results favour our preferred diagnosis. If lab evidence of sepsis/ SIRS is lacking, we often fail to revise the diagnosis or treatment rather than using novel strategies or terms to reach a unequivocal diagnosis of sepsis (diagnosing culture negative sepsis, for example).

Though we all know that blood culture remains the “gold standard” for the diagnosis of neonatal sepsis, our approach to blood culture practices is far from ideal. We often do not send a proper blood culture, or do not trust a culture report. 

There are many categories of neonatologists with regard to their approach towards blood culture!

altogether doubts the practical usefulness of blood culture in treatment of neonatal sepsis, and chooses not to send this particular investigation at all. They argue that the culture yield is too low to be helpful to them. The fact that culture is not a cheap investigation may also influence their conviction.

The pessimist

sends the blood culture, often just because it is in their protocol or routine work up list. They have lost their trust in blood culture results a long time ago, and choose to treat neonates purely based on their clinical experience/trust. They may accept a positive blood culture if it matches with their clinical diagnosis, but otherwise choose to ignore the report!

The hypocrite

sends blood cultures religiously, and although the yield is low, chooses to hope for the best and gets excited every time a positive report is available. 

The optimist

ensures a proper blood culture is sent in every suspected case of blood culture, and trusts the report fully. They show courage to take action based on the blood culture, whether the report is positive or negative.

The steadfast

Though in practice there is so much variation in the attitudes of neonatologists (as mentioned above) we all like to be the steadfast example in an ideal world. The question is whether all of us can alter/improve our clinical practice to match such standards or not. There are a lot of valid questions that we have to answer and convince ourselves of before we have any scope in changing existing practices:

What is the supposed sensitivity of the blood culture in neonatal sepsis?

How can we improve the sensitivity of blood cultures?

How early can I take action based on the culture report?

Should I need to step down treatment if the baby is clinically improving?

Contrary to popular belief, blood culture in neonatology is supposedly 100% sensitive!¹ That relies on at least 1ml of blood being inoculated, and the neonate having a bacteremia level of a minimum 4 CFU (colony forming units) per milliliter. Fortunately, or unfortunately, in a typical case of neonatal sepsis, the extent of bacteremia is > 100 CFU per milliliter.² The detection rates of modern blood culture methods are becoming even more accurate, retaining high sensitivity even when the bacteremia is low level, such as at 1-4 CFU/ ml. Though it can be argued that, in the unusual case of a neonate with ultra-low bacteremia (that is < 1 CFU/ml), the sensitivity decreases significantly, such a situation is often clinically irrelevant. In all practical aspects, for a baby with ultralow bacteremia, the natural body defense mechanisms would be sufficient to clear the bacterial infection, and an inevitable dose of antibiotics (for 48 hours or so) should do the job.

This naturally raises the question of “why are culture yields traditionally so low?”. The simple answer is that we are miserly with respect to the amount of blood we are inoculating! Believe it or not, we often end up submitting < 0.5 ml of blood for blood culture. Decreasing the amount of blood from 1 ml to 0.5 ml would decrease the sensitivity by as much as 40%. A 0.1 or 0.2 ml sample of blood sent for the purpose of blood culture almost makes the process a waste of time and resources. One of the perceived reasons behind not sending a 1 ml blood sample for culture is the practical difficulty in bloodletting. Though 1 ml is a significant amount in very preterm babies, the clinical implications make it an absolute necessity. The problem can be partially solved by taking the first 1 ml of blood after accessing the IV cannula/ or during sampling for the culture, with all other investigations being given second priority. This means that, for an occasional baby, the RFT or PT/ INR etc. may have to be postponed. A clear written order in the case sheet mentioning this and the amount of blood needed is also found to be helpful.

Another condition that makes blood culture less sensitive is prior antibiotic use. Ensuring that blood culture samples are taken at first contact or before administering the first dose of antibiotics may be the only way around this problem. This problem is greatest in outpatient births and referred cases of neonates. However, even in those cases, ensuring a proper amount of blood for culture often greatly improves the situation.

False positives or contamination in blood culture can be easily avoided by ensuring proper aseptic precautions are taken during sampling. Proper use of skin disinfectants such as 2% chlorhexidine gluconate in 70% isopropyl alcohol (2% alcoholic chlorhexidine), or even 10% povidone iodine is mandatory. Creating a specific “cannulation set” is a rewarding and simple practice (a sterile tray with cotton swabs and other necessities for cannulation), as this ensures a sterile surface/field which significantly decreases the contamination risks.

Trusting blood culture reports and taking the necessary actions are steps which are as important as ensuring proper blood culture collection technique. This means that, once a positive culture is received and sensitivity is available, we should downgrade antibiotics to the narrowest spectrum antibiotic clinically appropriate. This is necessary even if the baby’s condition was very poor to begin with and this is currently improving on an empirically sensitive broad-spectrum antibiotic. 

Trusting the blood culture if the report is sterile is often a more demanding process. There is plenty of evidence to show that it is safe to take action over a 48-hour blood culture report.4,5 A practical approach is to stop antibiotics if the blood culture is sterile and the baby is doing well after 48 hours. If the baby is still symptomatic at 48 hours (and you are still not able to rule out infection as a cause for the symptoms), it is wise to consider inflammatory markers (CRP, Procalcitonin etc) and to stop antibiotics if these fall within an acceptable range.

Preventing the unnecessary use of antibiotics is the need of the hour, and an essential step in providing quality care for sick neonates. Antibiotic usage in a culture negative vulnerable neonate has been shown to increase the incidence of necrotizing enterocolitis, bronchopulmonary dysplasia and death.

Though a 100 percent theoretical sensitivity of blood culture in neonatal sepsis is difficult to achieve in routine clinical practice, we can definitely improve neonatal outcomes with the above-mentioned quality improvement initiatives. This is like targeting a zero incidence of health care associated infection (HAI) rate in the NICU: we won’t succeed unless we try, we won’t try if we don’t believe, and if we don’t believe then nothing will ever happen.

Schelonka RL, Chai MK, Yoder BA, Hensley D, Brockett RM, Ascher DP. Volume of blood required to detect common neonatal pathogens. J Pediatr. 1996;129(2):275–278.

Sabui T, Tudehope DI, Tilse M. Clinical significance of quantitative blood cultures in newborn infants. J Paediatr Child Health. 1999;35(6):578–581.

Cantey JB and Baird SD. Ending the Culture of Culture-Negative Sepsis in the Neonatal ICU. Pediatrics. 2017;140(4):e20170044

Kaiser J, Cassat J, Lewno M. Should Antibiotics be Discontinued at 48 Hours for Negative Late-Onset Sepsis Evaluations in the Neonatal Intensive Care Unit? J Perinatol.2002;22:445–447.

Dretvik T, Solevåg AL, Finvåg A, Størdal EH, Størdal K, Klingenberg C. Active antibiotic discontinuation in suspected but not confirmed early-onset neonatal sepsis – a quality-improvement initiative. Acta Paediatr. 2020; Accepted Author Manuscript: doi:10.1111/apa.15202.

Ting JY, Synnes A, Roberts A, Deshpandey A, Dow K, Yoon EW et al. Association between antibiotic use and neonatal mortality and morbidities in very low-birthweight infants without culture-proven sepsis or necrotizing enterocolitis. JAMA Pediatr. 2016;170(12):1181–1187.

100% Sensitivity in Blood Culture for Neonatal Sepsis:  Myth or Reality?

Department of Nephrology - Aster Medcity, Kochi

Haisam Bin Abdul Kader, MD

MD, DNB, MRCP (UK), SCE Nephrology (UK), FASN, Department of Nephrology - Aster Medcity, Kochi

Vinod Kumar K

MD, DNB, DM, FRCP, FASN, Department of Pathology – Aster Medcity, Kochi

V N Unni

MD, Department of Pathology – Aster Medcity, Kochi

Nanda Kachare, MD

MD, DM, Department of Nephrology - Aster Medcity, Kochi

Bipi Prasannan

A 15-year-old male presented with acute glomerulonephritis, preceded by a history of sore throat and fever. He had features of acute rheumatic fever and echocardiographic evidence of severe mitral regurgitation and aortic regurgitation. He had proteinuria, haematuria and renal failure; renal biopsy showed diffuse exudative endocapillary proliferative glomerulonephritis. Simultaneous occurrence of acute glomerulonephritis and rheumatic fever in the same patient is very rare. He responded to treatment with steroids and his renal functions recovered over three months.

Acute post-streptococcal glomerulonephritis (APSGN) and acute rheumatic fever (RF) are both well-recognized non suppurative sequelae of group A beta hemolytic streptococcus infections.¹ The serotypes of group A Streptococci can be divided into those with rheumatogenic and nephritogenic potential.² Post-streptococcal glomerulonephritis and rheumatic fever have different epidemiology and immunological features; their concurrent development in the same patient is very rare,³ because of their different pathophysiologic mechanisms.

A 15-year-old male presented with history of fever of three weeks duration, associated with a sore throat. Twenty days after the onset of fever, he noticed puffiness of the face followed by progressive worsening of oedema involving the rest of the body. He had bilateral pedal oedema and abdominal distension, associated with dark-coloured urine and reduced urine output. He had arthralgia involving both knee joints. Urine examination showed numerous RBCs and proteinuria; Serum creatinine was 1.8mg/dl. There was a weight gain of 8 kg.

On admission to our center, the patient was febrile, and blood pressure was 130/88 mm Hg corresponding to the 95th centile). He had pallor, facial and pedal oedema. He had gradual worsening of dyspnoea and tachypnoea, and a grade 3/6 pansystolic murmur in the mitral area radiating to the axilla. 

Investigations revealed Haemoglobin: 9.9 g/dl, WBC count: 8100 /cu mm, Platelet count: 242000/cu mm, ESR: 44mm at 1 hour, CRP: 103.5mg/dl, serum creatinine: 1.77mg/dl and serum albumin: 2.8 g/dl. Urine analysis showed albumin 2+ and microscopic haematuria. Urine protein (24hr) was 6.1 g. The patient had elevated ASO titres (>800) and hypocomplementemia (serum C3:45 mg/dl). A chest X-ray showed bilateral blunting of the costophrenic angles, suggestive of bilateral pleural effusion. An electrocardiogram showed a prolonged PR interval (0.32 seconds). Renal failure worsened rapidly; serum creatinine increased to 6.9 mg/dl over 7 days. In view of this, a renal biopsy was done after initiation of dialysis. Blood and urine cultures were sterile, and a throat swab showed no growth.

The renal histology showed features of diffuse exudative proliferative glomerulonephritis with neutrophilic exudates (Figs 1A, 1B, 1C). Immunofluorescence revealed granular capillary wall staining for IgG (3+) and C3 (2+). There were no crescents. The picture was consistent with post-infectious glomerulonephritis.

A 2D echocardiogram (figs 2A, 2B) showed dilated left atrium and left ventricle, right coronary cusp prolapse and severe aortic regurgitation. The aortic valve annulus was 2.2 cm. The anterior mitral leaflet was thickened, and there was severe eccentric mitral regurgitation with chordal rupture (mitral annulus 3.4cm). A trans-oesophageal echocardiogram confirmed the findings. As he had one major and two minor criteria of modified Jones criteria for rheumatic fever, he was diagnosed to have acute rheumatic fever. Infective endocarditis was ruled out, as repeated blood cultures were sterile and there was no evidence of vegetations from the echocardiogram. 

As the patient had diffuse proliferative glomerulonephritis, with massive proteinuria and renal failure, he was started on Prednisolone 60mg/day (1.5 mg/kg/day). Renal functions improved gradually after initiation of steroids. He was treated with oral Furosemide and antihypertensives. Benzathine Penicillin (1.2 MIU injection intramuscularly) was advised every 3 weeks. He improved remarkably on treatment with steroids. The aortic regurgitation (AR) improved from severe AR to mild AR over ten days; however moderate mitral regurgitation persisted. At the time of discharge, serum creatinine was 2.9 mg/dl. On follow-up at three months, serum creatinine was 1.1mg%, and ESR 15mm/hr. Urine analysis showed 5 RBCs/hpf and no albuminuria. A 2D echocardiogram showed persistence of mild mitral and aortic regurgitation. Steroids were tapered and stopped within three months.

APSGN can affect individuals of any age, but typically occurs usually between the ages of 5 and 15 years⁵; males are affected twice as often as females. Post-infectious glomerulonephritis is associated with a previous skin or throat infection by a group A streptococcus (Streptococcus pyogenes), or occasionally group C or G streptococci. Pyoderma associated APSGN occurs more frequently in summer. A review estimated that over 470,000 cases of APSGN occur annually worldwide. 97% of these cases are in less developed countries, with an annual incidence that ranges from 9.5 to 28.5 per 100,000 individuals7. Studies from India have reported that APSGN constitutes about 6 to 8% of all renal biopsy specimens.

Rheumatic fever can occur at any age, although most cases occur in children aged 5 to 15 years7. There are about 233,000 deaths worldwide attributable to rheumatic fever or rheumatic heart disease each year7. The mean incidence of RF is 19 per 100,000 school-aged children worldwide10. Rheumatic fever occurs more frequently in winter months.

Two antigens have been implicated as potential causes of APSGN: the glycolytic enzyme identified as glyceraldehyde-3-phosphate dehydrogenase, and streptococcal proteinase exotoxin B (SPEB, zymogen), both of which activate the alternate pathway of the complement system8. APSGN occurs due to the antibody-mediated response to bacterial infection, typically with a nephritogenic strain of Streptococcus pyogenes, which results in glomerular deposition and/or in-situ formation of immune complexes; a glomerular inflammatory response ensues with leukocyte infiltration and complement activation⁶. Nephritogenic strains associated with the development of APSGN include M types 1, 4, 12, 15 (causing throat infection and ASPGN) and 2, 42, 49, 55, 57, 60 (causing skin infection and ASPGN).

A streptococcal strain capable of causing a well-documented pharyngitis is almost always capable of causing rheumatic fever11. Many M types are associated with RF, including 1, 3, 5, 6, 11, 12, 14, 17, 18, 19, 24, 27, 29, 30, 32, and 4112.The lack of specific rheumatogenic strains may explain the relatively high risk of recurrent disease with new streptococcal infections, in contrast to poststreptococcal glomerulonephritis, in which only a few “nephritogenic” strains appear to be capable of inducing the disease, and hence recurrent disease is uncommon.

Acute rheumatic fever is caused by the mechanism of molecular mimicry. M protein and the hyaluronate capsule cause inflammation by inducing cross-reacting autoantibodies against human tissue proteins, stimulated by cell-mediated immunity in genetically predisposed patients. Early recognition of acute rheumatic fever is very important, because of the possibility of developing rheumatic heart disease if not treated appropriately.

Co-existent acute rheumatic fever and post streptococcal glomerulonephritis were observed in our patient. PSGN and RF rarely coincide, as has been previously described.¹,³ Simultaneous occurrence of APSGN and acute RF was first reported in 1981. Since then, seventeen cases have been reported. Most of the cases had acute RF preceding, or after the event of APSGN. Only six out of seventeen patients had simultaneous occurrence of acute RF and APSGN, as seen in our case13. The explanation for the co-occurrence might be that certain strains have both nephritogenic and rheumatogenic potential (e.g. M types 1 and 12), which can result in the occurrence of both conditions.³ Although some serotypes are both rheumatogenic and nephritogenic, it cannot be said with certainty whether a single pharyngeal infection resulted in both APSGN and acute RF in this case; however the possibility of a single infection causing both PSGN and rheumatic fever cannot be ruled out. We could not isolate the organism on throat swab culture.

Mitral insufficiency is frequently seen in patients with concurrent acute RF and APSGN, however only 2 cases of aortic insufficiency have been reported so far with these conditions. Our patient had both mitral and aortic insufficiency

In patients associated with acute RF, focal and mesangial proliferative glomerulonephritis has been reported; diffuse exudative proliferative glomerulonephritis which is typical of APSGN is rare; our patient had diffuse proliferative GN

Co-existence of RF and APSGN in the same patient is very rare. Awareness of infection risk and prevention strategies at the grass roots level is essential to lessen the burden of post-infectious glomerulonephritis in our country. 

https://firebasestorage.googleapis.com/v0/b/article-app-d985d.appspot.com/o/blogmedia%2F1732167787523amj_Nov2020%20p84.jpg?alt=media&token=075ef0b1-a65a-4a21-87d6-bdc63af62411

Kula S,Saygili A, F. Sedef T, Olgunturk R. Acute Poststreptococcal Glomerulonephritis and Acute Rheumatic Fever in the Same Patient: a Case Report and Review of the Literature. Anadolu KardiyolDerg.2003;3:272-4.

Bisno AL. Group A streptococcal infections and acute rheumatic fever. N Engl J Med. 1991;325(11):783–93.

Bisno AL. The coexistence of acute rheumatic fever and acute glomerulonephritis. Arthritis Rheum.1989;32:230-32. 

Augustina J, Vilija C, Paulius K, Karolis A. Acute poststreptococcal glomerulonephritis and acute rheumatic fever: An uncommon coincidence. Ann PediatrCardiol. 2016;9(3):268.

Nasr  SH, Fidler ME, Valeri AM, et al. Postinfectious glomerulonephritis in the elderly. J Am Soc Nephrol.2011;22:187-95.

Rodríguez-Iturbe B, Haas M. Post-streptococcal glomerulonephritis. In Ferretti JJ, Stevens DL, Fischetti VA, editors. Streptococcus pyogenes, Basic Biology to Clinical Manifestations. Oklahoma City: University of Oklahoma Health Sciences Center;2016. p. 869–92.

Rodriguez-Iturbe B, Musser JM. The current state of poststreptococcal glomerulonephritis. J Am Soc Nephrol. 2008;19(10):1855-64.

Cunningham MW. Pathogenesis of group A streptococcal infections. Clin Microbiol Rev. 2000;13(3):470–511.

de Dassel JL, Ralph AP, Carapetis JR. Controlling acute rheumatic fever and rheumatic heart disease in developing countries: are we getting closer? CurrOpinPediatr. 2015;27(1):116–23.

. 	Whitnack E, Bisno L. Rheumatic fever and other immunologically-mediated cardiac diseases. In: Parker CW, editor. Clinical immunology. Philadelphia: W. B. Saunders Co; 1980. Vol 2, p. 894-929.

. 	Metzgar D, Zampolli A. The M protein of group A Streptococcus is a key virulence factor and a clinically relevant strain identification marker. Virulence. 2011;2(5):402–12.

Martin WJ, Steer AC, Smeesters PR, Keeble J, Inouye M, Carapetis J, et al. Post-infectious group A streptococcal autoimmune syndromes and the heart. Autoimmun Rev.2015;14:710-25.

Watanabe, T. Atypical Clinical Manifestations of Acute Poststreptococcal Glomerulonephritis. In: Sharma Prabhakar, editor. An Update on Glomerulopathies – Clinical and Treatment Aspects. Croatia: In Tech publishing; 2011. p151-168.

Acute Post-streptococcal Glomerulonephritis and Acute Rheumatic Fever, Co-existing in the Same Patient

Medcare Women and Children Hospital, Dubai

Dr Roopa R

Dr Shiva H

Dr Geetha B

Dr Raji C

Monochorionic twin, twin to twin transfusion syndrome, selective intra uterine restriction.

There are no conflicts of interest to report and no external funding sources.

Monochorionic twin pregnancies, by virtue of vascular anastomoses, are at risk of unique complications. These include Twin-To-Twin Transfusion Syndrome (TTTS), Selective Intrauterine Growth Restriction (sIUGR), and Twin Reverse Arterial Perfusion (TRAP) sequence. Vascular anastomoses are present in every monochorionic placenta; these represent a state of imbalance in the shunting of blood, or an abnormality in the nature of anatomising vessels, which forms the basis for these unique clinical entities. The extreme circumstances of these complications eventually lead to single foetal demise in such twins. The intra-uterine demise of one fetus results in the acute transfer of intravascular volume from the co-twin to the dying twin (rescue transfusion), resulting in exsanguination with accompanying hypotension, anaemia, death and ischaemic cerebrovascular insults to the co-twin. The demise of one foetus in a monochorionic gestation is associated with co-foetal demise in 12–25% of cases, and a risk of neurological abnormalities in 18–25% of surviving infants.1

Umbilical artery Doppler flow is the parameter which best reflects the difference in growth restriction between monochorionic and dichorionic twins; Changes in flow within the umbilical artery are closely related to clinical changes and outcomes. Foetuses with positive diastolic flow have a benign prognosis, whilst foetuses with intermittent absent or reversed diastolic flow have a high risk of intra-uterine foetal demise, and consequently ischaemic damage, especially parenchymal brain damage, to the normally growing twin. Under such circumstances, selective termination of one foetus optimizes the chances of survival of the co-twin. Selective foetal reduction is known to improve the perinatal outcome in the extreme situations caused by this complication of monochorionicity. 2,3 Interventional procedures such as intra-cardiac injection of cardio toxic agents like potassium chloride cannot be carried out in monochorionic pregnancies, because of the risk of a drug being transferred to the co-twin via the anastomosing vessels. Selective termination in monochorionic pregnancies instead requires ablation of the blood flow in the umbilical cord, to prevent acute intra-foetal transfusion. 
We present here a case of TTTS with sIUGR, for which growth restriction typing was completed according to the classification criteria proposed by Gratacos et al.4 TTTS was classified based on the Quintero system.5


A 39-year-old gravida 2, para 1, living 1 (previous LSCS) patient was referred to the foetal medicine unit of MWCH, for a second opinion on a monochorionic diamniotic twin pregnancy with TTTS at 20 weeks of gestation. Her blood group was rhesus A positive. All recent menstrual cycles were regular and there was no significant medical, surgical and family history. The patient had conceived naturally. At a scan at 12 weeks of gestation, a diagnosis of monochorionic diamniotic twin pregnancy was made. The foetuses were concordant for liquor growth and aneuploidy markers. The first trimester screen was negative for aneuploidies, with all biochemical parameters within the normal limits. 

On referral, Monochorionicity was confirmed through the ultrasound findings of a single placenta, a thin intervening membrane and lack of a lambda sign. A detail target scan with Doppler study and foetal echo was carried out. Our findings were a monochorionic twin pregnancy at a gestational age of 20 weeks and 3 days, with an anterior common placenta (gestational age was assigned as per the last menstrual period). The twins were discordant for liquor, bladder, growth and Doppler flow. Twin A had no measurable liquor pocket, suggestive of anhydramnios, and the single deepest pocket of liquor for twin B was 8.7cm.The bladder was absent for twin A and distended for twin B. Estimated foetal weights were 225 g and 356 g for twin A and B respectively. The weight discordancy between the foetuses was 37%.

november-2020

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